DigitalUM :: Browsing by Subject "Fibrosis"

Browsing by Subject "Fibrosis"

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Open Access
Abnormal collagen deposition in synovia after collagen type V immunization in rabbits
(Murcia : F. Hernández, 2008) Tsuzuki Ichicawa Ogido, Luciana; Walcy Rosolia, Teodoro; Pereira Velosa, Ana Paula; De Oliveira, Cristiane Carla; Roger Parra, Edwin; Capelozzi, Vera Luiza; Hajime Yoshinari, Natalino
Sinovitis in Scleroderma (SSc) is rare, usually aggressive and fully resembles rheumatoid arthritis. Experimental models of SSc have been used in an attempt to understand its pathogenesis. Previous studies done in our laboratory had already revealed the presence of a synovial remodeling process in rabbits immunized with collagen V. To validate the importance of collagen type V and to explore the quantitative relationship between this factor and synovia remodeling as well as the relationship between collagen type V and other collagens, we studied the synovial tissue in immunized rabbits. Rabbits (N=10) were immunized with collagen V plus Freund’s adjuvant and compared with animals inoculated with adjuvant only (N=10). Synovial tissues were submitted to histological analysis, immunolocalization to collagen I, III and V and biochemical analysis by eletrophoresis, immunoblot and densitometric method. The synovial tissue presented an intense remodeling process with deposits of collagen types I, III and V after 75 and 120 days of immunization, mainly distributed around the vessels and interstitium of synovial extracellular matrix. Densitometric analysis confirmed the increased synthesis of collagen I, III and V chains (407.69±80.31; 24.46±2.58; 70.51±7.66, respectively) in immunized rabbits when compared with animals from control group (164.91±15.67; 12.89±1.05; 32±3.57) (p<0.0001). We conclude that synovial remodeling observed in the experimental model can reflect the articular compromise present in patients with scleroderma. Certainly, this experimental model induced by collagen V immunization will bring new insights in to pathogenic mechanisms and allow the testing of new therapeutic strategies to ameliorate the prognosis for scleroderma patients.
Open Access
Anti-inflammatory and antifibrotic effects of resveratrol in the lung
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Conte, Enrico; Fagone, Evelina; Fruciano, Mary; Gili, Elisa; Iemmolo, Maria; Vancheri, Carlo
Resveratrol, a natural polyphenolic molecule with several biological activities, is a well recognized anti-oxidant, anti-aging and cancer chemopreventive agent. Moreover, resveratrol anti-inflammatory and antifibrotic properties have been demonstrated both in vitro and in different animal models of inflammatory pathologies, including bowel and liver diseases. We review the evidence of resveratrol protective role in respiratory diseases such as acute lung injury, asthma, chronic obstructive pulmonary disease and lung fibrosis. We conclude that resveratrol and its derivatives may act as a therapeutic agents in respiratory diseases and pertinent clinical trials should be performed.
Open Access
Cytokines and pulmonary inflammatory and immune diseases
(Murcia : F. Hernández, 1999) Xing, Z.; Jordana, M.; Gauldie, J.; Wang, J.
Cytokines are important soluble signalling molecules that dictate and coordinate inflammatory and immune responses. Further understanding the role of cytokines in the pathobiologic mechanisms of pulmonary inflammatory and immune diseases holds the key to the development of effective prophylactic and therapeutic strategies. In the last several years, the use of models of human pulmonary diseases established either in normal adult animals, mice deficient for a given immune cell type or cytokine, or mice engineered to overexpress a given cytokine, has remarkably facilitated our understanding of the mechanisms operating in human disease. Cytokines that are involved in pulmonary inflammatory and immune conditions may be generally divided into groups of pro-inflammatory, antiinflammatory and growth-stimulatory cytokines. While pro-inflammatory cytokines can be detrimental under such severe conditions as endotoxemia and fibrosis, they are required in host resistance against infectious agents. Anti-inflammatory cytokines play an important role in controlling the extent of tissue inflammatory/irnmune responses. Overexpression of growth-stimulatory cytokines are often directly associated with tissue fibrotic responses. In this review, the findings attained from experimental models by us and others were discussed with emphasis on cellular and histopathologic alterations, cytokine-mediated molecular mechanisms and the prospects of cytokine-based therapeutic strategies. Due to the restricted space, we chose to focus only on models for endotoxic lung, endotoxemia, acute pulmonary infections by extracellular Gram-negative bacteria, chronic pulmonary infections by intracellular myco-bacteria, allergic airways inflammation and pulmonary fibrosis.
Open Access
Evolutionary trade-offs in kidney injury and repair
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Lei, Yutian; Anders, Hans Joachim
Evolutionary medicine has proven helpful to understand the origin of human disease, e.g. in identifying causal roles of recent environmental changes impacting on human physiology (environmentphenotype mismatch). In contrast, diseases affecting only a limited number of members of a species often originate from evolutionary trade-offs for usually physiologic adaptations assuring reproductive success in the context of extrinsic threats. For example, the G1 and G2 variants of the APOL1 gene supporting control of Trypanosoma infection come with the trade-off that they promote the progression of kidney disease. In this review we extend the concept of evolutionary nephrology by discussing how the physiologic adaptations (danger responses) to tissue injury create evolutionary trade-offs that drive histopathological changes underlying acute and chronic kidney diseases. The evolution of multicellular organisms positively selected a number of danger response programs for their overwhelming benefits in assuring survival such as clotting, inflammation, epithelial healing and mesenchymal healing, i.e. fibrosis and sclerosis. Upon kidney injury these danger programs often present as pathomechanisms driving persistent nephron loss and renal failure. We explore how classic kidney disease entities involve insufficient or overshooting activation of these danger response programs for which the underlying genetic basis remains largely to be defined. Dissecting the causative and hierarchical relationships between danger programs should help to identify molecular targets to control kidney injury and to improve disease outcomes.
Open Access
Histopathology of Duchenne muscular dystrophy in correlation with changes in proteomic biomarkers
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Zweyer, Margit; Sabir, Hemmen; Dowling, Paul; Gargan, Stephen; Murphy, Sandra; Swandulla, Dieter; Ohlendieck, Kay
Duchenne muscular dystrophy is an inherited disorder of early childhood that affects multiple systems in the body. Besides late-onset cardio-respiratory syndrome and various body-wide pathophysiological changes, X-linked muscular dystrophy is primarily classified as a disorder of the skeletal musculature. This is reflected by severe histopathological alterations in voluntary contractile tissues, including progressive fibre degeneration, fat substitution, reactive myofibrosis and chronic inflammation. The underlying cause for dystrophinopathy are genetic abnormalities in the DMD gene, which can result in the almost complete loss of the membrane cytoskeletal protein dystrophin, which triggers the collapse of the dystrophin-associated glycoprotein complex and disintegration of sarcolemmal integrity. This in turn results in an increased frequency of membrane micro-rupturing and abnormal calcium ion fluxes through the impaired plasmalemma, which renders muscle fibres more susceptible to enhanced proteolytic degradation and necrosis. This review focuses on the complexity of skeletal muscle changes in X-linked muscular dystrophy and outlines cell biological and histological alterations in correlation to proteomewide variations as judged by mass spectrometric analyses. This includes a general outline of sample handling, subcellular fraction protocols and modern proteomic approaches using gel electrophoretic and liquid chromatographic methods for efficient protein separation prior to mass spectrometry. The proteomic profiling of the dystrophic and highly fibrotic diaphragm muscle is described as an example to swiftly identify novel proteomic markers of complex histopathological changes during skeletal muscle degeneration. The potential usefulness of new protein markers is examined in relation to key histopathological hallmarks for establishing improved diagnostic, prognostic and therapy-monitoring approaches in the field of dystrophinopathy.
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Molecular mechanisms of postoperative atrial fibrillation in patients with obstructive sleep apnea
(Wiley, 2023-04-28) López Gálvez, Raquel; Rivera Caravaca, José Miguel; Mandaglio Collados, Darío; Lahoz, Álvaro; Carpes, Marina; Arribas, José María; Cánovas López, Sergio; Lip, Gregory Y. H.; Marín, Francisco; Martínez Cáceres, Carlos Manuel; Orenes-Piñero, Esteban; Hernández Romero, Diana; Cirugía, Pediatría y Obstetricia y Ginecología
Obstructive sleep apnea (OSA) promotes atrial remodeling and fibrosis, providing a substrate for atrial fibrillation (AF). Herein, we investigate the pathophysiological mechanisms of AF in association with OSA in a cohort of cardiac surgery patients. A prospective study including patients undergoing cardiac surgery. Biomarkers reflective of AF pathophysiology (interleukin [IL-6], C-reactive protein [CRP], von Willebrand factor [vWF], N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity Troponin T [hs-TnT], and Galectin-3 [Gal-3]) was assessed by functional or immunological assays. miRNAs involved in AF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Using atrial tissue samples, fibrosis was assessed by Masson's trichrome. Connexin 40 and 43 (Cx40; Cx43) were evaluated by immunolabeling. Fifty-six patients (15 with OSA and 41 non-OSA) were included in this hypothesis-generating pilot study. OSA group had a higher incidence of postoperative AF (POAF) (46.7% vs. 19.5%; p = .042), presented an increased risk of POAF (OR 3.61, 95% CI 1.01–12.92), and had significantly higher baseline levels of NT-proBNP (p = .044), vWF (p = .049), Gal-3 (p = .009), IL-6 (p = .002), and CRP (p = .003). This group presented lower levels of miR-21 and miR-208 (both p < .05). Also, lower Cx40 levels in POAF and/or OSA patients (50.0% vs. 81.8%, p = .033) were found. The presence of interstitial fibrosis (according to myocardial collagen by Masson's trichrome) was raised in OSA patients (86.7% vs. 53.7%, p = .024). Several biomarkers and miRNAs involved in inflammation and fibrosis were dysregulated in OSA patients, which together with a higher degree of interstitial fibrosis, altered miRNA, and Cxs expression predisposes to the development of a substrate that increases the AF risk.
Open Access
MRL/MpJ mice show unique pathological features after experimental kidney injury
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Shiozuru, Daichi; Ichii, Osamu; Kimura, Junpei; Nakamura, Teppei; Ali Elewa, Yaser Hosny; Otsuka-Kanazawa, Saori; Kon, Yasuhiro
Clarification of the renal repair process is crucial for developing novel therapeutic strategies for kidney injury. MRL/MpJ mice have a unique repair process characterized by low scar formation. The pathological features of experimentally injured MRL/MpJ and C57BL/6 mouse kidneys were compared to examine the renal repair process. The dilation and atrophy of renal tubules were observed in folic acid (FA)-induced acute kidney injury (AKI) in both strains, and the histopathological injury scores and number of interleukin (IL)-1F6-positive damaged distal tubules and kidney injury molecule 1 (KIM-1)-positive damaged proximal tubules drastically increased 1 day after AKI induction. However, KIM-1- positive tubules and the elevation of serum renal function markers were significantly fewer and lower, respectively, in MRL/MpJ mice at days 2 and 7 after AKI. After traumatic kidney injury (TKI) via needle puncture, severe tubular necrotic lesions in the punctured area and fibrosis progressed in both strains. Indices for fibrosis such as aniline blue-positive area, number of alpha smooth muscle actin-positive myofibroblasts, and messenger RNA expression levels of Tgfb1 and Mmp2 indicated lower fibrotic activity in MRL/MpJ kidneys. Characteristically, only MRL/MpJ kidneys manifested remarkable calcification around the punctured area beginning 7 days after TKI. The pathological features of injured MRL/MpJ and C57BL/6 kidneys differed, especially those of kidneys with mild proximal tubular injuries after FA-induced AKI. Lower fibrotic activity and increased calcification after TKI were observed in MRL/MpJ kidneys. These findings clarified the unique pathological characteristics of MRL/MpJ mouse kidneys and contribute to understanding of the renal repair process after kidney injury
Open Access
Myocardial Remoding: Mechanisms and Translational Implications
(2022-05) Roncalli, Jerome; Tronchère, Helene; Lax Pérez, Antonio Manuel; Kunduzova, Oxaca; Medicina
Open Access
Oxidized regenerated cellulose does not prevent the formation of experimental postoperative perineural fibrosis assessed by digital analysis
(Murcia: F. Hernández, 2010) Hernández Cortés, Pedro; Peregrina, Magdalena; Aneiros Fernández, José; Tassi, Mohamed; Pajares López, Miguel; Toledo, Miguel; O’Valle, Francisco
Introduction: It is difficult to prevent and treat intra- and peri-neural fibrosis after peripheral nerve surgery. Many authors have attempted to develop and verify the effectiveness of substances to decrease the formation of adherences in different tissues. Material and Methods: this study aimed to assess the effectiveness of a barrier of oxidized regenerated cellulose (ORC) to reduce adherence and perineural fibrosis in a model of surgical perineural induced fibrosis in rat sciatic nerve in 40 rats. After tissue aggression, the nerve of the right rear limb was wrapped in ORC and the left limb served as control. Animals were killed at 3 and 6 weeks, and nerves and muscle mass were extracted en bloc. Connective tissue was quantified by conventional histopathological techniques and Fibrosis HR® automatic image analysis. Results: No significant differences were found in intra- or peri-neural induced fibrosis between control nerves (6.88% and 8.90%, respectively) and treated nerves (6.57% and 9.90%) at 3 or 6 weeks (10.41% and 12.51% in controls; 11.85% and 15.72% in treated nerves). Inflammatory phenomena and granulomatous reactions were more frequent in treated animals. Conclusions: ORC conferred no advantage in prevention of nerve fibrosis and might have interfered with healing.
Open Access
Pathological changes in the liver of a senescence accelerated mouse strain (SAMP8): A mouse model for the study of liver diseases
(Murcia : F. Hernández, 2004) Ye, X.; Meeker, H.C.; Kozlowski, P.B.; Wegiel, J.; Wang, K.C.; Imaki, H.; Carp, R.I.
Liver disease is characterized by fatty liver, hepatitis, fibrosis and cirrhosis and is a major cause of illness and death worldwide. The prevalence of liver diseases highlights the need for animal models for research on the mechanism of disease pathogenesis and efficient and cost-effective treatments. Here we show that a senescence-accelerated mouse strain (SAMP8 mice), displays severe liver pathology, which is not seen in senescence-resistant mice (SAMR1). The livers of SAMP8 mice show fatty degeneration, hepatocyte death, fibrosis, cirrhotic changes, inflammatory mononuclear cell infiltration and sporadic neoplastic changes. SAMP8 mice also show abnormal liver function tests: significantly increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, titers of murine leukemia virus are higher in livers of SAMP8 than in those of SAMR1 mice. Our observations suggest that SAMP8 mouse strain is a valuable animal model for the study of liver diseases. The possible mechanisms of liver damage in SAMP8 mice are also discussed.
Open Access
Pathophysiological role of cytoglobin, the fourth globin in mammals, in liver diseases
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Thuy, Le Thi Thanh; Hai, Nguyen Thi Thanh; Hai, Hoang; Kawada, Norifumi
Cytoglobin (Cygb), a stellate cell-specific globin, has recently drawn attention due to its association with liver fibrosis and cancer. In human and rodent livers, Cygb is expressed only in stellate cells and can be utilized as a marker to distinguish stellate cells from hepatic fibroblast-derived myofibroblasts. Loss of Cygb accelerates liver fibrosis and cancer development despite its etiology in mouse models of chronic liver injury. This review discusses the current perception of the distribution, regulation and function of Cygb with regard to liver diseases, with an emphasis on its role in tumorigenesis. Further investigation of Cygb may shed new light on the biology of organ carcinogenesis.
Open Access
Phenytoin activates SMAD3 phosphorylation and periostin expression in drug-induced gingival enlargement
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Kim, Shawna S.; Nikoloudaki, Georgia; Darling, Mark; Rieder, Michael J.; Hamilton, Douglas W.
Drug-induced gingival enlargement (DIGE) is a fibrotic condition associated with systemic administration of the anti-epileptic drug, phenytoin. We have previously demonstrated that periostin, which is transforming growth factor-beta (TGF-β) inducible gene, is upregulated in various fibrotic conditions including gingival enlargement associated with nifedipine. The objective of this study was to assess periostin expression in phenytoin-induced gingival enlargement (PIGE) tissues and to investigate the mechanisms underlying periostin expression. Human PIGE tissues were assessed using Masson’s trichrome, with cell infiltration and changes in extracellular matrix composition characterized through labeling with antibodies to periostin, phospho-SMAD 3, TGF-β, as well as the macrophage markers CD68 and RM3/1. Using human gingival fibroblasts (HGFs) in vitro, we examined the pathways through which phenytoin acts on fibroblasts. In PIGE tissues, which demonstrate altered collagen organization and increased inflammatory cell infiltration, periostin protein was increased compared with healthy tissues. p-SMAD2/3, the transcription factor associated with canonical TGF-β signaling, is localized to the nuclei in both gingival fibroblasts and oral epithelial cells in PIGE tissues, but not in healthy tissue. In vitro culture of HGFs with 15 and 30 μg/ml of phenytoin increased periostin protein levels, which correlated with p-SMAD3 phosphorylation. Inhibition of canonical TGF-β signaling with SB431542 significantly reduced phenytoin induction of SMAD3 phosphorylation and periostin expression in HGFs. Analysis of PIGE tissues showed a subset of CD68 stained macrophages were TGF-β positive and that RM1/3 regenerative macrophages were present in the tissues. Our results demonstrate that phenytoin up-regulates periostin in HGFs in a TGF-β-dependent manner.
Open Access
Potential therapeutic effect of SO2 on fibrosis.
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2019) Wang, Xin Bao; Cui, Hong; Du, Jun Bao
Fibrosis is a pathological feature of most chronic diseases and leads to the dysfunction of various organs. However, there is currently no effective method for treating fibrosis. In recent years, a small gas, sulfur dioxide (SO2), which can be generated endogenously in mammals, has been found to have vasorelaxation activity, improve cardiac function and decrease myocardial injury. Endogenous SO 2 also mediates the process of fibrosis. Inhibition of endogenous SO 2 can aggravate small pulmonary artery remodeling and abnormal collagen accumulation. SO 2 treatment significantly improves pulmonary fibrosis and pulmonary arterial remodeling. Overexpression of the key enzymes associated with endogenous SO 2 generation, aspartate aminotransferase (AAT) 1 and AAT2, mimics the effect of SO 2 on the down-regulation of collagen synthesis, while AAT1 or AAT2 knockdown aggravates abnormal collagen accumulation in vascular smooth muscle cells (VSMCs). SO 2 also improves myocardial fibrosis induced by myocardial infarction or diabetes in rats, and inhibits myocardial fibroblast proliferation and migration by the extracellular signal- regulated protein kinase pathway. The mechanisms underlying the inhibition of fibrosis by SO 2 are related to its antioxidant effect, anti-inflammation effect, improvement in cardiac function, and cell proliferation inhibition. Therefore, SO 2 has a potential therapeutic effect on fibrosis.
Open Access
Presence of perivenular elastic fibers in nonalcoholic steatohepatitis Fibrosis Stage III
(Murcia : F. Hernández, 2008) Nakayama, Hirofumi; Itoh, Hiroyuki; Kunita, Satoko; Kuroda, Naoto; Hiroi, Makoto; Matsuura, Hideo; Yasui, Wataru; Enzan, H.
Elastic fibers appear in extensive old fibrotic foci in general. We examined an association between hepatic fibrosis stage and the presence of perivenular elastic fibers in nonalcoholic steatohepatitis (NASH). A total of 48 liver needle biopsy specimens were used, taken from 48 cases with NASH. Fibrosis Stage (Brunt E, et al. Am. J. Gastroenterol. 1999) of the cases was as follows; six Fibrosis Stage I, twenty-two Fibrosis Stage II, and twenty Fibrosis Stage III. We examined Orcein stain sections in all of the liver needle biopsy specimens. In all twenty Fibrosis Stage III cases, perivenular elastic fiber bundles were observed. In contrast, perivenular elastic fibers were detected only in one of the six Fibrosis Stage I and two of the twenty-two Fibrosis Stage II cases. In liver needle biopsy specimens of NASH, detection of perivenular elastic fibers is useful in deciding Fibrosis Stage III.
Open Access
Role of fibrosis-related genes and pancreatic duct obstruction in rat pancreatitis models: Implications for chronic pancreatitis
(Murcia : F. Hernández, 2007) Miyauchi, M.; Suda, K.; Kuwayama, C.; Abe, H.; Kakinuma, C.
Human chronic pancreatitis is characterized by irreversible fibrosis, whereas pancreatic fibrosis in animal models is reversible. In this study, we compare the development of pancreatic fibrosis in the dibutyltin dichloride (DBTC) model, WBN/Kob rats and bile ductligated (BDL) rats. DBTC (8 mg/kg) was administered to LEW rats, and the pancreas was histopathologically investigated sequentially. Male and female WBN/Kob rats aged 4, 6 and 8 months were also examined. BDL rats were prepared by ligation of the bile duct at the duodenal portion and sacrificed at 3 or 7 days after ligation. Fibrosis in the DBTC model peaked after 1 week and was limited to the areas around the pancreatic ducts after 2 weeks, and was composed of both type I and type III collagen. In contrast, fibrosis in male WBN/Kob rats peaked at age 4 months, expanded into intralobular area, and was composed of type III collagen. It exhibited almost no type I collagen and a marked tendency to regress. Pancreatic fibrosis in BDL rats was somewhat difficult to induce and required increased stimulation. This suggests that fibrosis in human biliary pancreatitis may gradually form based on weak, continuous stimulation. We conclude that type I collagen may be involved in the progression of irreversible fibrosis. The imbalance between synthesis and degradation of extracellular matrix molecules or degree of stimulation over a certain period may lead to pancreatic fibrosis. Gene expressions of prolyl hydroxylase and tissue inhibitors of matrix metalloproteinase-2 were elevated.
Open Access
Role of myofibroblasts during normal tissue repair and excessive scarring:Interest of their assessment in nephropathies
(Murcia : F. Hernández, 2000) Badid, C.; Mounier, N.; Costa, A.M.A.; Desmoulière, A.
Following injury, tissue repair process takes place involving inflammation, granulation tissue formation and scar constitution. Granulation tissue develops from the connective tissue surrounding the damaged area and contains vessels, inflammatory cells, fibroblasts and myofibroblasts. Myofibroblasts play an important role in many tissue injuries and fibrocontractive diseases. The process of normal wound repair after tissue injury follows a closely regulated sequence including the activation and the proliferation of fibroblastic cells. In pathological situations, the normal resolution stages are abrogated and the proliferation of myofibroblasts continues, inducing excessive accumulation of extracellular matrix. The differentiation of fibroblastic cells into myofibroblasts is an early event in the development of tissue fibrosis. Myofibroblastic cells express smooth muscle cytoskeletal markers (asmooth muscle actin in particular) and participate actively in the production of extracellular matrix. The evaluation of myofibroblast differentiation in renal biopsies would be useful for histopathologists to appreciate the intensity of tissue injury and particularly to predict the long term outcome of some nephropathies. Immunohistochemical studies for a-smooth muscle actin should be made systematically in renal tissue biopsies. Myofibroblastic differentiation appears to play a significant role in the progression of renal failure and seems to be a useful marker of progressive disease.
Open Access
The anti-fibrotic effect of liver growth factor is associated with decreased intrahepatic levels of matrix metalloproteinases 2 and 9 and transforming growth factor beta 1 in bile duct-ligated rats
(Murcia : F. Hernández, 2008) Díaz-Gil, Juan J.; García-Monzón, Carmelo; Rúa, Carmen; Martín Sanz, Paloma; Cereceda, Rosa M.; Machín, Celia; Fernández Martínez, Amalia; Miquilena-Colina, María E.; García Cañero, Rafael
Liver growth factor (LGF), a mitogen for liver cells, behaves as an anti-fibrotic agent even in extrahepatic sites, but its mechanistic basis is unknown. We aimed to determine the intrahepatic expression pattern of key modulators of liver fibrosis in bile ductligated rats (BDL) after injection of LGF. BDL rats received either LGF (4.5 μg/ratXdose, two doses/week, at time 0 or 2 or 5w after operation, depending on the group (BDL+LGF groups, n=20) or saline (BDL+S groups, n=20). Groups were compared in terms of fibrosis (histomorphometry), liver function (aminopyrine breath test), matrix metalloproteinases MMP-2 and MMP-9, transforming growth factor beta 1 (TGF-ß1) and liver endoglin content (Western blotting), and serum tissue inhibitor of metalloproteinases 1 (TIMP-1) levels (ELISA). In BDL+LGF rats, the fibrotic index was significantly lower at 5w, p=0.006, and at 8w, p=0.04, than in BDL+S rats. Liver function values in BDL+LGF rats were higher than those obtained in BDL+S rats (80% at 5w and 79% at 8w, versus 38% and 29%, p<0.01, taking healthy controls as 100%). Notably, in BDL+LGF rats the intrahepatic expression levels of both MMPs were lower at 2w (MMP-2, p=0.03; MMP-9, p=0.05) and 5w (MMP-2, p=0.05, MMP-9, p=0.04). In addition, the hepatic TGF-ß1 level in BDL+LGF rats was lower at 2w (36%, p=0.008), 5w (50%) and 8wk (37%), whereas intrahepatic endoglin expression remained constant in all BDL rats studied. LGF ameliorates liver fibrosis and improves liver function in BDL rats. The LGF-induced anti-fibrotic effect is associated with a decreased hepatic level of MMP-2, MMP-9 and TGF-ß1 in fibrotic rats.
Open Access
The contribution of type II pneumocytes and alveolar macrophages to fibroplasia processes in the course of enzymatic lung injury
(Murcia : F. Hernández, 1997) Sulkowska, M.; Sulkowski, S.
The aim of the paper was to evaluate mutual relations in the system of alveolar macrophage (AM) - type 11 pneumocyte (PII) - interstitium of alveolar septa, in the course of experimental lung emphysema in rats subjected to BCG vaccine effect. Administration of BCG vaccine resulted in the cumulation of AM within pulmonary alveoli. These cells exhibited morphological features of increased activity. Intratracheal papain injection induced intralobular emphysema changes, partly generalized, in the animal lungs. The emphysematous changes, with domination of interalveolar septum atrophy, were accompanied by foca1 accumulation of collagen and elastin. Fibroplasia processes were strongly pronounced in BCG- and papain-treated animals. The areas of connective tissue fibres cumulation revealed indistinctness of the boundary line between PII and the interstitium in some places. Anchorage of collagen fibres and microfibrillary structures were observed in the cytoplasm of PII. The morphological examinations of AM - fibroblasts co-cultures as well as the evaluation of the uptake of 3 ~ - thymidine did not show any significant differences between respective co-cultures of fibroblasts and AM isolated both from the lungs of control and experimental animals (treated with BCG or papain, and BCG+papain). However, a significant growth was noted in 3 ~ - thymidine uptake between fibroblast cultures realized with or without cells isolated from the lungs. The results obtained suggest the possibility of active participation of PII and AM in fibroplasia processes in the course of lung rebuilding after papain administration and in pathological states of the pulmonary tissue, particularly when they are accompanied by increased activity of alveolar macrophages. They also support the inflammatory-repair hypothesis in the development of emphysematous changes.
Open Access
Tissue and molecular events in human conjunctival scarring in ocular cicatricial pemphigoid
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Razzaque, M. S.; Foster, C. S.; Ahmed, A. R.
Detail ed histomo rph ometric analysis of human conjunctiva l biopsy specimens has convincingly demonstrated that tissue remodeling of the extracellular matri x (EC M) is an esse nti al and dy nami c process associated with conjuncti val sca rring in ocul ar cicatricial pemphi go id (OCP). The co njun cti va l sca rring ofte n eventuall y results in impaired vision and/or blindness. The molecul ar mechanisms of conjunctival scarring are not compl etely und erstood. Acc umulating evidence indicates that the earl y phase of conjunctival fibrosis is linked with an immuno-inflammatory process medi ated by cy tokines released by ac tiva ted conjunctiv al cells and/or by infiltrating cells. Fibrogenic cytokines secreted by infl ammatory cells and fibroblasts might acti vely be in vo lve d in remode lin g o f th e matri x within th e conjunctival stroma, possibly by regul ating the altered metabolism of matrix proteins.
Open Access
Los tres pilares del tratamiento en fibrosis quística: antibioterapia, fisioterapia, nutrición/ Federación Española contra la Fibrosis Quística (ed.): Reseña bibliográfica.
(Murcia : Servicio de Publicaciones de la Universidad de Murcia, 2011-09-05) Jiménez Ávila, Bernabé