DigitalUM :: Browsing by Subject "Extracellular matrix"

Browsing by Subject "Extracellular matrix"

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Open Access
A simple method for the differential characterization of alveoli and alveolar ducts in injured lungs
(Murcia : F. Hernández, 2005) Negri, E.M.; Omar, E.D.; Mori, S.S.; Rodrigues, N.R.D.; Barbas, C.S.V.; Saldiva, P.H.N.; Dolhnikoff, M.
Rationale and hypothesis: Previous studies evaluating the histoarchitecture of distal airspaces have been shown to be limited by the difficulty in adequately differentiating alveoli and alveolar ducts. This limitation has been specially noticed in studies addressing lung recruitment and in situations of diffuse alveolar damage (DAD), where generic nominations for distal airspaces had to be created, such as “peripheral airspaces” (PAS) and “large-volume gas-exchanging airspaces” (LVGEA). Elastic stains have been largely used to describe normal lung structures. Weigert’s resorcin-fuchsin staining (WRF) demarcates the thickened free portions of the ductal septum facilitating its recognition. We hypothesized that this staining could help in differentiating alveoli from alveolar ducts in distorted lung parenchyma. Material and Methods: Samples of control lungs and of DAD lungs induced by mechanical ventilation (VILI) were stained with hematoxylin-eosin (H&E) and with WRF. Using morphometry we assessed the volume proportion of alveoli, alveolar ducts and LVGEA in control and VILI lungs. Results: WRF stained VILI lungs showed a significant decrease in the volume proportion of LVGEA and alveoli and a significant increase in the volume proportion of alveolar ducts when compared to H&E stained samples. Conclusion: We conclude that WRF staining is useful to distinguish alveolar ducts from alveoli in a DAD model, and suggest that it should be routinely used when morphometric studies of lung parenchyma are performed.
Open Access
Butylated hydroxytoluene induces type-V collagen and overexpression of remodeling genes/proteins in experimental lung fibrosis
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Martins, Vanessa; Teodoro, Walcy Rosolia; Pereira Velosa, Ana Paula; Andrade, Priscila; Farhat, Cecília; Fabro, Alexandre Todorovic; Capelozzi, Vera Luiza
Anomalous histoarchitecture with increased levels of type-V collagen (Col V) in lungs of human idiopathic pulmonary fibrosis (IPF) and bleomycin (BLM) airway-centered interstitial fibrosis suggest that this collagen can be a possible trigger involved in the pathogenesis of these diseases. Butylated hydroxytoluene (BHT) injury model revealed a distal involvement of lung parenchyma with significant endothelial injury and fibrotic response, contrasting with the BLM airway-centered insult. We undertook this study to analyze whether BHT alters distal airway/alveolar epithelial cells (AECs) and extracellular matrix (ECM) signaling involved in the initiation and progression of pulmonary fibrosis in a different pathway concerning overexpression of Col V. Female mice C57BL/6 (n=6) were instilled intraperitoneally with 400mg/kg of BHT dissolved in 1 mL of corn oil and euthanized at day 14 or 21 after BHT administration. Morphometry, immunohistochemistry and transmission electron microscopy were performed to characterize microscopic and submicroscopic changes of AECs and endothelial cells through transforming growth factor beta (TGF-β) basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) expression. Immunofluorescence and immunogold electron microscopy were performed to characterize Col V. Quantitative polymerase chain reaction (qPCR) was used to confirm differential levels of RNA messenger. BHT lungs showed marked fibrotic areas and hyperplastic AECs. The alveolar damage caused destruction of elastic fibers and a critical increase of Col V in ECM of distal lung parenchyma. Fibrogenesis-promoting markers TGF-β, bFGF and VEGF were also overexpressed in situ, coinciding with up-regulation in remodeling enzymes, growth factors, cytokines, transduction and transcription genes. BHT alters distal lung parenchyma signaling involved in pulmonary fibrosis highlighted similarities to human IPF in a pathway involving Col V arising as a promissory model to identify effective therapeutic targets.
Open Access
Changes in vascular extracellular matrix composition during decidual spiral arteriole remodeling in early human pregnancy
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Smith, Samantha D.; Choudhury, Ruhul H.; Matos, Patricia; Horn, James A.; Lye, Stephen J.; Dunk, Caroline E.; Aplin, John D.; Jones, Rebecca L.; Harris, Lynda K
Uterine spiral arteriole (SA) remodeling in early pregnancy involves a coordinated series of events including decidual immune cell recruitment, vascular cell disruption and loss, and colonization by placentalderived extravillous trophoblast (EVT). During this process, decidual SA are converted from narrow, muscular vessels into dilated channels lacking vasomotor control. We hypothesized that this extensive alteration in SA architecture must require significant reorganization and/or breakdown of the vascular extracellular matrix (ECM). First trimester decidua basalis (30 specimens) was immunostained to identify spiral arterioles undergoing trophoblast-independent and -dependent phases of remodeling. Serial sections were then immunostained for a panel of ECM markers, to examine changes in vascular ECM during the remodeling process. The initial stages of SA remodeling were characterized by loss of laminin, elastin, fibrillin, collagen types III, IV and VI from the basement membrane, vascular media and/or adventitia, and surrounding decidual stromal cells. Loss of ECM correlated with disruption and disorganization of vascular smooth muscle cells, and the majority of changes occurred prior to extensive colonization of the vessel wall by EVT. The final stages of SA remodeling, characterized by the arrival of EVT, were associated with the increased mural deposition of fibronectin and fibrinoid. This study provides the first detailed analysis of the spatial and temporal loss of ECM from the walls of remodeling decidual SA in early pregnancy.
Open Access
Characterization of organotypic keratinocyte cultures on de-epithelialized bovine tongue mucosa
(Murcia : F. Hernández, 2002) Hildebrand, H.C.; Häkkinen, L.; Wiebe, C.B.; Larjava, H.S.
Organotypic cultures have been used to study epithelial cell behavior for many years. The aim of this study was to develop an organotypic culture method that better mimics the three-dimensional morphology of interdigitating rete ridges and connective tissue papillae and that also conserves the basement membrane zone (BMZ). Bovine tongue mucosa connective tissue, separated from epithelium after 1M NaCl incubation, was used as o rganotypic culture substratum for different human keratinocyte cell lines. Organotypic cultures were characterized by electron and immunofluorescence microscopy for expression of integrin subunits and extracellular matrix components. While spontaneously immortalized mucosal keratinocytes produced highly irregular stratified organotypic cultures, the normal human epidermal keratinocytes (NHEK) demonstrated culture morphology that resembled in vivo epidermis. However, in this model, the histomorphology, expression of differentiation markers involucrin, keratin 10 and 14, and integrins varied significantly between the cell lines. Some cultures appeared to have an extended survival since they were maintained up to 40 days without histological signs of degeneration. The ultrastructure of the BMZ including hemidesmosomes was similar to the normal dermo-epidermal junction. Extracellular matrix molecules, including tenascin, laminin-1 and -5, were expressed in the cultures demonstrating their secretion solely by keratinocytes. Distribution and expression of integrins in NHEK cultures was similar to that seen in vivo skin with the exception of additional expression of a5ß1 and avß6 integrins. Organotypic NHEK cultures show similarities to normal stratified epithelium and are potentially useful for multiple applications for studies on epithelial cell behavior in vitro.
Open Access
Constitutive and regulated expression of vitronectin
(Murcia : F. Hernández, 1997) Seiffert, D.
Tissue homeostasis depends on spatially and temporally controlled expression of multifunctional adhesive glycoproteins and their cellular counter receptors, and on a tight regulation of proteolytic enzyme systems. The adhesive glycoprotein vitronectin (Vn) not only regulates adhesive events, but also controls a number of these proteolytic enzyme cascades, including the complement, coagulation, and fibrinolytic systems. However, understanding of the biological functions of this molecule is complicated due to it's conformationally lability and its tendency to selfassociate. While plasma Vn is monomeric and lacks exposure of conformationally sensitive epitopes, platelet and tissue-associated Vn are believed to be conformationally altered and multimeric. The latter forms express a functional repertoire distinct from plasma Vn. While little Vn immunoreactivity is detectable in most normal tissues, increased depositions of Vn have been observed in areas of tissue injury and necrosis. Tissue Vn was believed to be plasma-derived, but recent studies indicate that extrahepatic cells have the biosynthetic potential to produce Vn and that its synthesis can be regulated under inflammatory conditions. Here, the constitutive and regulated expression of Vn, its locations in tissues and interaction with other matrix molecules are reviewed and their implications for the functions of this molecule are discussed.
Open Access
Decorin and biglycan expression: its relation with endothelial heterogeneity
(Murcia: F. Hernández, 2011) Calabrese, Graciela C.; Gazzaniga, Silvina; Oberkersch, Roxana; Wainstok, Rosa
Decorin and biglycan proteoglycans play important roles in the organization of the extracellular matrix, and in the regulation of cell adhesion and migration. Given morphological and functional endothelial heterogeneity, information is needed regarding whether endothelial cells (ECs) from different vascular beds possess different profiles of proteoglycan constituents of the basement membranes. Here, we report that endothelia from different murine organs and EC lines derived thereof produce and secrete different patterns of proteoglycans. A faint colocalization between decorin and PECAM/CD31 was found on tissue sections from mouse heart, lung and kidney by immunofluorescence. Three EC lines derived from these organs produced decorin (100-kDa) and its core protein (45-kDa). Extracellular decorin recognition in culture supernatant was only possible after chondroitin lyase digestion suggesting that the core protein of secreted proteoglycan is more encrypted by glycosaminoglycans than the intracellular one. Heart and lung ECs were able to produce and release decorin. Kidney ECs synthesized the proteoglycan and its core protein but no secretion was detected in culture supernatants. Although biglycan production was recorded in all EC lines, secretion was almost undetectable, consistent with immunofluorescence results. In addition, no biglycan secretion was detected after EC growth supplement treatment, indicating that biglycan is synthesized, secreted and quickly degraded extracellularly by metalloproteinase-2. Low molecularmass dermatan sulfate was the predominant glycosaminoglycan identified bound to the core protein. ECs from different vascular beds, with differences in morphology, physiology and cell biology show differences in the proteoglycan profile, extending their heterogeneity to potential differences in cell migration capacities.
Open Access
Determinants of axonal regeneration
(Murcia : F. Hernández, 1997) Frisén, J.
Axons often regrow to their targets and lost functions may be restored after an injury in the peripheral nervous system. In contrast, axonal regeneration is generally very limited after injuries in the central nervous system, and functional impairment is usually permanent. The regenerative capacity depends on intrinsic neuronal factors as weil as the interaction of neurons with other cells. Glial cells may, in different situations, either support or inhibit axonal growth. This review discusses the molecular mechanisms that are involved in promoting and inhibiting axonal regeneration in the nervous system after injuries.
Open Access
Dynamic interactions of the extracellular matrix
(Murcia : F. Hernández, 1996) Slater, M.
The extracellular matrix (ECM) is a dynamic assemblage of interacting molecules that reorganise and regulate cell functions in response to endogenous and exogenous stimulii. Matrix components may affect cell behaviour directly or indirectly through growth factor sequestration and transmembrane signalling, by controlling the speed of various molecules through the ECM, and the access of growth factors, hormones and neurotransmitters to the cell surface.
Open Access
Engineering vascular grafts from decellularized plants: Advances and challenges
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Merna Nick; Biología Celular e Histología
Small-caliber vascular grafts (<6 mm diameter) are critical for coronary and peripheral bypass surgeries, yet developing functional substitutes remains challenging. Autologous vessels are ideal but often unavailable or of poor quality. Synthetic grafts, such as expanded polytetrafluoroethylene (ePTFE) and Dacron, have high failure rates at small diameters due to thrombosis, intimal hyperplasia, and compliance mismatch. Tissue-engineered vascular grafts (TEVGs) aim to overcome these issues by providing a biocompatible scaffold with an endothelial lining. Decellularized plant tissues have recently gained attention as natural scaffolds for TEVGs due to their structural similarity to human vasculature. Leaves and stems provide an extracellular matrix (ECM) primarily composed of cellulose, which is biocompatible, porous, and non-thrombogenic. These scaffolds are cost-effective, scalable, and ethically uncontroversial. Decellularized parsley stems or leatherleaf leaves, for instance, can be recellularized with endothelial and smooth muscle cells (SMCs) to create small-diameter grafts that support endothelialization and withstand physiological pressures. Perfusion bioreactors further enhance the functionality of plant-based grafts by simulating physiological conditions. Pulsatile flow and pressure stimulate endothelial cell alignment, reducing thromb-ogenicity, while mechanical stimulation promotes SMC maturation and ECM deposition, improving graft strength and compliance. This review summarizes recent advances in plant-based vascular grafts and perfusion bioreactor conditioning, compares their performance to conven-tional grafts, and highlights remaining challenges. Decellularized plant scaffolds, with their inherent vascular architecture and biocompatibility, show promise as natural templates for small-caliber vascular grafts. However, further research is needed to address key challenges such as standardization, mechanical optimization, and long-term in vivo validation to facilitate their clinical application
Open Access
Ex vivo and in vivo modulatory effects of umbilical cord Wharton’s jelly stem cells on human oral mucosa stroma substitutes
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2015) Alfonso-Rodríguez, C.A.; González-Andrades, E.; Jaimes-Parra, B.D.; Fernández-Valadé, R. s; Campos, A.; Sánchez-Quevedo, M. C.; Alaminos, M.; Garzon, I.
Novel oral mucosa substitutes have been developed in the laboratory using human umbilical cord Wharton’s jelly stem cells -HWJSC- as an alternative cell source. In the present work, we have generated human oral mucosa substitutes with oral mucosa keratinocytes and HWJSC to determine the influence of these cell sources on stromal differentiation. First, acellular and cellular stroma substitutes and bilayered oral mucosa substitutes with an epithelial layer consisting of oral mucosa keratinocytes -OM samplesor HWJSC -hOM- were generated. Then, tissues were analyzed by light and electron microscopy, histochemistry and immunohistochemistry to quantify all major extracellular matrix components after 1, 2 and 3 weeks of ex vivo development, and OM and hOM were also analyzed after in vivo grafting. The results showed that bioengineered oral mucosa stromas displayed an adequate fibrillar mesh. Synthesis of abundant collagen fibers was detected in OM and hOM after 3 weeks, and in vivo grafting resulted in an increased collagen synthesis. No elastic or reticular fibers were found. Glycoprotein synthesis was found at the epithelialstromal layer when samples were grafted in vivo. Finally, proteoglycans, decorin, versican and aggrecan were strongly dependent on the in vivo environment and the presence of a well-structured epithelium on top. The use of HWJSC was associated to an increased synthesis of versican. These results confirm the usefulness of fibrinagarose biomaterials for the generation of an efficient human oral mucosa stroma substitute and the importance of the in vivo environment and the epithelialmesenchymal interaction for the adequate differentiation of the bioengineered stroma.
Open Access
Extracellular matrix components in atherosclerotic arteries of Apo E/LDL receptor deficient mice: An immunohistochemical study
(Murcia : F. Hernández, 2004) Ström, Å.; Ahlqvist, E.; Franzé, Adela; Heinegård, D.; Hultghrdh-Nilsson, A.
During accelerated vascular remodeling such as in atherosclerosis, the composition of the extracellular matrix becomes altered. The matrix components of the diseased artery influence cellular processes such as adhesion, migration and proliferation. Furthermore, in atherosclerosis, the inability of the cells within the lesion to produce a mechanically stable matrix may lead to plaque rupture. In this immunohistochemical study of atherosclerotic mice aorta, we have reviewed the presence of ECM components with roles in maintaining tissue structure and function. These components include osteopontin and COMP as well as the leucine rich repeats proteins decorin, PRELP, and fibromodulin. Immunohistochemistry demonstrated presence of osteopontin, COMP, decorin, PRELP and fibromodulin in lesion areas of ApoE/LDLr deficient mice. Some advanced lesions exhibited areas of cartilage-like morphology and were shown to represent cartilage by their content of the cartilage specific proteins collagen II and aggrecan. The results suggest that cartilageassociated cell/collagen binding ECM proteins may be involved in the pathogenesis of atherosclerosis.
Open Access
Extracellular matrix, biotensegrity and tumor microenvironment. An update and overview
(F. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología., 2012) Noguera, Rosa; Nieto, Olga Alicia; Tadeo, Irene; Fariñas, Fernando; Álvaro, Tomás
The extracellular matrix (ECM) constitutes a three-dimensional network that surrounds all cells, organs and tissues in the body. It forms a biophysical filter for protection, nutrition and cell innervation, as well as the medium for facilitating immune response, angiogenesis, fibrosis and tissue regeneration. It is the mechanism by which mechanical forces are transmitted to the basement membrane which, through the integrins, supports the tensegrity system and activates the epigenetic mechanisms of the cell. A review and update on current knowledge on this topic reveals how disturbance of the ECM leads to a loss of efficient filtering, nutrition, elimination, and cell denervation functions, in addition to loss of regeneration capacity and disorders in mechanotransduction. Furthermore, such disturbance results in a loss of substrate, and with it the ability to provide a proper immune response against tumor, toxic and infectious agents. Reciprocal communication between ECM stromal and parenchymatous cells directs gene expression. The oncogenic capacity of the stroma derives from the associated cells as well as from the tumor cells, the angiogenic microenvironment and from an alteration in tensegrity; all of which are dependent on the ECM. It has been shown that the malignant phenotype is reversible by correction of the altered cues of the ECM.
Open Access
Influence of a hypercholesterolemic diet on the collagen composition of the bladder wall extracellular matrix in rats
(F. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología., 2012) Nunes, R.L.V.; Bruschini, H.; Utsunomia, K.; Silveira, M.A.; Teodoro, W.R.; Leite, K.R.M.; Srougi, M.
Purpose: To investigate the effects of hypercholesterolemic diet on the collagen composition of urinary bladder wall. Materials and methods: Forty-five female 4-week-old Wistar rats were divided into three groups: 1) control group fed a normal diet (ND); 2) model of bladder outlet obstruction (BOO) group fed a ND; and 3) group fed a HCD (1.25% cholesterol). Total serum cholesterol, LDL cholesterol and body weight were assessed at baseline. Four weeks later, group 2 underwent a surgical procedure resulting in a partial BOO, while groups 1 and 3 underwent a sham similar surgical procedure. Six weeks later, all animals had their bladders removed; serum cholesterol and LDL cholesterol levels and body weights were measured. Morphological and morphometric analysis was performed by Picrosirius staining and collagen types I and III were identified by immunofluorescence. Statistical analysis was completed and significance was considered when p<0.05. Results: Rats fed an HCD exhibited a significant increase in LDL cholesterol levels (p<0.001) and body weight (p=0.017), when compared to the groups fed a ND during the ten-week study period. Moreover, the HCD induced morphological alterations of the bladder wall collagen, regarding thin collagen fibers and the amounts of type III collagen when compared to the control group (p=0.002 and p=0.016, respectively), resembling the process promoted in the BOO model. Conclusions: A hyper-cholesterolemic diet in Wistar rats promoted morphological changes of the bladder types of collagen, as well as increases in body weight and LDL cholesterol.
Open Access
Integrated extracellular matrix signaling in mammary gland development and breast cancer progression
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Zhu, Jieqing; Xiong, Gaofeng; Trinkle, Christine; Xu, Ren
Extracellular matrix (ECM), a major component of the cellular microenvironment, plays critical roles in normal tissue morphogenesis and disease progression. Binding of ECM to membrane receptor proteins, such as integrin, discoidin domain receptors, and dystroglycan, elicits biochemical and biomechanical signals that control cellular architecture and gene expression. These ECM signals cooperate with growth factors and hormones to regulate cell migration, differentiation, and transformation. ECM signaling is tightly regulated during normal mammary gland development. Deposition and alignment of fibrillar collagens direct migration and invasion of mammary epithelial cells during branching morphogenesis. Basement membrane proteins are required for polarized acinar morphogenesis and milk protein expression. Deregulation of ECM proteins in the long run is sufficient to promote breast cancer development and progression. Recent studies demonstrate that the integrated biophysical and biochemical signals from ECM and soluble factors are crucial for normal mammary gland development as well as breast cancer progression.
Open Access
Integrin-mediated signal transduction pathways
(Murcia : F. Hernández, 1999) Cary,L.A.; Han, D.C.; Guan, J.L.
Integrins serve as adhesion receptors for extracellular matrix proteins and also transduce biochemical signals into the cell. They regulate a variety of cellular functions, including spreading, migration, proliferation and apoptosis. Many signaling pathways downstream of integrins have been identified and characterized and are discussed here. In particular, integrins regulate many protein tyrosine kinases and phosphatases, such as FAK and Src, to coordinate many of the cell processes mentioned above. The regulation of MAP kinases by integrins is important for cell growth or other functions, and the putative roles of Ras and FAK in these pathways are discussed. Phosphatidylinositol lipids and their modifying enzymes, particularly PI 3-kinase, are strongly implicated as mediators of integrinregulated cytoskeletal changes and cell migration. Similarly, actin cytoskeleton regulation by the Rho family of GTPases is coordinated with integrin signaling to regulate cell spreading and migration, although the exact relationship between these pathways is not clear. Finally, intracellular pH and calcium fluxes by integrins are suggested to affect a variety of cellular proteins and functions.
Open Access
Long-term type 1 diabetes alters the deposition of collagens and proteoglycans in the early pregnant myometrium of mice
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Favaro, Rodolfo R.; Raspantin, Priscila R.; Salgado, Renato M.; Forte, Zuleica B.; Zorn, Telma M.T.
troduction: We have previously shown that long-term type 1 diabetes affects the structural organization, contractile apparatus and extracellular matrix (ECM) of the myometrium during early pregnancy in mice. Objective: This study aimed to identify which myometrial ECM components are affected by diabetes, including fibril-forming collagen types I, III and V, as well as proteoglycans, decorin, lumican, fibromodulin and biglycan. Methods: Alloxaninduced type 1 diabetic female mice were divided into subgroups D1 and D2, formed by females that bred 90- 100 and 100-110 days after diabetes induction, respectively. The deposition of ECM components in the myometrium was evaluated by immunohistochemistry/immunofluorescence. Results: The subgroup D1 showed decreased deposition of collagen types I and III in the external muscle layer (EML) and decreased collagen types III and V in the internal muscle layer (IML). Collagen types I and III were decreased in both muscle layers of the subgroup D2. In addition, increased deposition of collagen types I and III and lumican as well as decreased collagen type V were observed in the connective tissue between muscle layers of D2. Lumican was decreased in the EML of the subgroups D1 and D2. Fibromodulin was repressed in the IML and EML of both D1 and D2. In contrast, decorin deposition diminished only in muscle layers of D2. No changes were noticed for biglycan. Conclusions: Subgroups D1 and D2 showed distinct stages of progression of diabetic complications in the myometrium, characterized by both common and specific sets of changes in the ECM composition.
Open Access
Lymphocyte interactions with the extracellular matrix of malignant cells in vítro: A morphological and immunocytochemical study
(Murcia : F. Hernández, 1993) Logothetou-Rella, H.
The interactions of lymphocytes with the glycosaminoglycans-protease-membrane extracellular matrix, produced by mixed cell cultures of normal with malignant cell clones, were examined. Pre-activated and activated heterologous peripheral lymphocytes were used. Co-cultures of activated lymphocytes with al1 cell types used, formed identical cell nodules. Histology of cell nodules showed that activated lymphocytes were cytolytic to pure normal or malignant cell clones. On the contrary, lymphocytes in nodules with mixed cell clones (normal with malignant cell clones) or embryonic cells, underwent degeneration changing the fusiform type tumor nodule into the adenoid type. The adenoid type cell nodule consisted of cells with high nuclear to cytoplasm ratio and mitotic activity. In addition, leukocyte common antigen was deposited in the extracellular matrix and on the cell membrane of target tumor cells. Pre-activated lymphocytes, in mixed cell cultures, failed to lyse the target tumor cells and underwent abnormal cell divisions, producing subsets similar to nuclear vlimata, which remained attached to the extracellular matrix. The morphological and immunocytochemical observations of lymphocytes were discussed and attributed to the presence of the specific extracellular matrix of glycosaminoglycans-proteasemembranes
Open Access
Matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms promote increase and remodeling of the collagen III and V in posterior tibial tendinopathy
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Diniz Fernandes, Tulio; Godoy Santos, Alexandre Leme; Santos, Maria Cristina; Pontin, Pedro; Alves Pereira, Caio Augusto; Justi Jardim, Yuri; Pereira Velosa, Ana Paula; Maffulli, Nicola; Teodoro, Walcy Rosolia; Capelozzi, Vera Luiza
Posterior tibial tendinopathy (PTT) can lead to acquired flatfoot in adults. Many patients develop PTT without any identifiable risk factors. Molecular changes in extracellular matrix (ECM) and matrix metalloproteinase (MMP) polymorphism may influence the risk of developing PTT. We aim to investigate the association between matrix metalloproteinase-1 (MMP1) and (MMP-8) gene polymorphisms with changes in collagen I, III and V in PTT. A case-control study with 22 patients and 5 controls was performed. The MMP-1 (2G/2G) and MMP-8 (T/T) genotypes were determined by PCR-restriction fragment length polymorphism. Tendon specimens were evaluated by a histologic semiquantitative score, immunofluorescence and histomorphometry for collagen I, III and V. Tendon specimens from PTT demonstrated marked distortion of the architecture with necrosis, large basophilic areas with disruption of the normal linear orientation of collagen bundles, infiltration of inflammatory cells, dystrophic calcification and ossification. Under immunofluorescence, PTT tendon specimens showed weak green fluorescence and diffuse distribution of collagen I fibers, but strong fluorescence of collagen III and V. The collagen I fibers were significantly decreased whereas an increase of collagen III and V were found in PTT compared to control groups. In addition, PTT group presented a significant association with MMP-1 and MMP-8 gene polymorphisms. Patients with PTT matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms presented an increase of the collagen III and V ratio, suggesting that the higher proportion in degenerated tendons could contribute to a decrease in the mechanical resistance of the tissue. Still, functional and association studies are needed to elucidate evident roles of MMPs in PTT.
Open Access
Mechanisms of neuroinflammation and inflammatory mediators involved in brain injury following subarachnoid hemorrhage
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Okada, Takeshi; Suzuki, Hidenori
Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disorder. Neuro- inflammation is a critical cause of brain injury following SAH in both acute and chronic phases. While accumulating evidence has shown that therapies targeting neuroinflammation exerted beneficial effects in experimental SAH, there is little clinical evidence. One of the factors making neuroinflammation complicated is that inflammatory signaling pathways and mediators act as protective or detrimental responses at different phases. In addition, biomarkers to detect neuro- inflammation are little known in clinical settings. In this review, first, we discuss how the inflammatory signaling pathways contribute to brain injury and other secondary pathophysiological changes in SAH. Damage-associated molecular patterns arising from mechanical stress, transient global cerebral ischemia, red blood cell breakdown and delayed cerebral ischemia following SAH trigger to activate pattern recognition receptors (PRRs) such as Toll-like receptors, nucleotide-binding oligomerization domain-like receptors, and receptors for advanced glycation end products. Most of PRRs activate common downstream signaling transcriptional factor nuclear factor-κΒ and mitogen-activated protein kinases, releasing pro-inflammatory mediators and cytokines. Next, we focus on how pro-inflammatory substances play a role during the course of SAH. Finally, we highlight an important inducer of neuroinflammation, matricellular protein (MCP). MCPs are a component of extracellular matrix and exert beneficial and harmful effects through binding to receptors, other matrix proteins, growth factors, and cytokines. Treatment targeting MCPs is being proved efficacious in pre- clinical models for preventing brain injury including neuroinflammation in SAH. In addition, MCPs may be a candidate of biomarkers predicting brain injury following SAH in clinical settings.
Open Access
Metastatic dormancy: a complex network between cancer stem cells and their microenvironment
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Bleau, Anne-Marie; Agliano, Alice; Larzabal, Leyre; Lopez de Aberasturi, Arrate; Calvo, Alfonso
Metastasis represents the major threat of cancer progression and generally emerges years after the detection of the primary tumor. An important ratelimiting step resides in cellular dormancy, where a disseminated tumor cell remains in a quiescent state at a remote organ. Herein we review the molecular mechanisms leading to tumor dormancy, mainly in regards to cellular quiescence and the tumor microenvironment. Based on the current published literature, we provide evidence that links the cancer stem cell (CSC) theory with dormancy and metastasis. Once a disseminated tumor cell reaches a target tissue, a tight regulation imposed by the foreign microenvironment will dictate the fate of these cells, which implies a balance in the secretion of soluble factors, modulation of the extracellular matrix and the angiogenic switch. We investigate thoroughly whether the CSC theory could also apply to metastasis initiation. In fact, the resistance of CSCs to therapy, leading to the minimal residual disease and cellular quiescence phenotypes, predisposes for the development of metastases. Finally, we describe the new technologies available for the identification of circulating tumor cells (CTCs), as well as their clinical relevance in dormancy of metastatic cancer patients.