DigitalUM :: Browsing by Subject "Myofibroblast"

Browsing by Subject "Myofibroblast"

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Open Access
Cytokeratin-positive subserosal myofibroblasts in gastroduodenal ulcer; another type of myofibroblasts
(Murcia : F. Hernández, 2006) Guo, L.; Kuroda, Naoto; Nakayama, Hiroyuki; Miyazaki, E.; Hayashi, Yoshihiro; Toi, M.; Hiroi, Makoto; Enzan, H.
To investigate the distribution and origin of alpha-smooth muscle actin (ASMA)-positive stromal cells in the perforation of human gastroduodenal ulcers. Perforative lesions of 24 surgically resected gastroduodenal ulcers were examined immunohistochemically for ASMA, HCD, CD34, CD31, CAM5.2 and HMW-CK, and double staining of ASMA and CAM5.2 was also performed. In addition, to determine the cell source of collagen, in situ hybridization of collagen I mRNA was performed. In the normal gastroduodenal wall, the reticular network of CD34-positive stromal cells was identified in the muscularis mucosa, submucosa, muscular propria, and subserosa. In the subepithelial area, many myofibroblasts were observed, whereas no CD34- positive stromal cells were seen. In areas neighboring ulcerative lesions, no CD34-positive stromal cells were observed, but a significant number of myofibroblasts were present there. In the deep layer of ulceration, numerous fusiform or stellate stromal cells strongly positive for ASMA and CAM5.2 were observed in the subserosal area around the perforation. In the same site, many cells co-expressing ASMA and CAM5.2 were identified by double staining. In contrast, in the surface layer of ulceration, stromal cells expressing only ASMA were observed. The cytokeratin-positive subserosal myofibroblastic cell in human gastroduodenal ulcer is a novel type of myofibroblast.
Open Access
Distribution and role of CD34-positive stromal cells and myofibroblasts in human normal testicular stroma
(Murcia : F. Hernández, 2004) Kuroda, Naoto; Nakayama, Hiroyuki; Miyazaki, E.; Hayashi, Yoshihiro; Toi, M.; Hiroi, Makoto; Enzan, H.
CD34-positive stromal cells are distributed in various organs including breast, Fallopian tubes, thyroid gland, colon, pancreas, and uterine cervix. To elucidate the distribution of CD34-positive stromal cells, smooth muscle cells, and myofibroblasts in normal human testis, we examined 48 testes obtained by autopsy and operation, including five fetal, one neonatal, and 42 adult cases without evident testicular lesions, using a streptavidin-biotin immunoperoxidase technique. The expression of alpha-smooth muscle actin (ASMA), hcaldesmon, CD34, and CD31 were immunohistochemically examined in all cases. The tunica albuginea and the inner layer of seminiferous tubules in adult testis were predominantly composed of myofibroblasts. Smooth muscle cells were also scattered throughout these sites in some cases. CD34-positive stromal cells were abundant, and they formed a reticular network around the seminiferous tubules and Leydig cells as well as the outer layer of seminiferous tubules. Moreover, myofibroblasts and the CD34 reticular network were already present in the testicular stroma during fetal or neonatal development. Double immunostaining of fetal, neonatal and adult testes using ASMA and CD34 confirmed that myofibroblasts and CD34-positive stromal cells were present in the inner and outer layers of peritubular tissue, respectively. This distribution and cytological identification was also confirmed by an ultrastructural study of four cases. Finally, CD34- positive stromal cells and myofibroblasts are major components of human testicular stroma.
Open Access
Immunophenotypical analyses of myofibroblasts in rat excisional wound healing: possible transdifferentiation of blood vessel pericytes and perifollicular dermal sheath cells into myofibroblasts
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Juniantito, Vetnizah; Izawa, Takeshi; Yuasa, Takahiro; Ichikawa, Chisa; Kuwamura, Mitsuru; Yamate, Jyoji
Cutaneous fibrosis after wound is evoked by myofibroblasts capable of producing collagen; the derivation and features remain to be investigated. Immunophenotypical characteristics of myofibroblasts were analysed in excisional rat wound healing, of which samples were obtained on post-wounding (PW) days 1 to 26. Myofibroblasts were characterized for expressions of intermediate cytoskeletons such as vimentin, desmin, and α-smooth muscle actin (α-SMA). To pursue the progenitor, immunolabeling analyses were performed using stromal-/bone marrow-stem cell markers (Thy-1 and A3). Myofibroblasts reacting to vimentin and α-SMA were first seen on PW day 5, then peaked on PW day 9 in granulation tissues, and gradually decreased in remodeling tissues; these immunopositive cells reacted simultaneously to Thy-1. Desmin-reacting cells were limited to newly-formed blood vessels in wound bed. The single/double immunolabelings revealed that pericytes (identified by positive reaction to PDGFR-ß and negative reaction to endothelial markers) in newly-developing blood vessels reacted to vimentin, α-SMA, Thy-1 and A3, and occasionally to desmin, and that perifollicular dermal sheath cells in the wound periphery showed increased expressions for vimentin, Thy-1 and A3. There is considerable immunophenotypical similarity between myofibroblasts (expressing vimentin, α-SMA and Thy-1), pericytes (reacting to vimentin, α-SMA, Thy-1 and A3) in newly-developing blood vessels, and perifollicular dermal sheath cells (reacting to vimentin, Thy-1 and A3). Collectively, myofibroblasts in rat cutaneous fibrosis are characterized by vimentin, α-SMA and Thy-1 expressions, and the cells might be generated from the pericytes or perifollicular dermal sheath cells in the lineage of stroma-/bone marrow-stem cells
Open Access
Inhibition of muscle fibrosis and improvement of muscle histopathology in dysferlin knock-out mice treated with halofuginone
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2013) Halevy, Orna; Genin, Olga; Barzilai-Tutsch, Hila; Pima, Yaniv; Levi, Oshrat; Moshe, Itai; Pines, Mark
Absence of, or loss-of-function mutations in the dysferlin gene (dysf) result in dysferlinopathy, characterized by increased muscle inflammation, collagen deposition and deterioration in muscle function. We evaluated halofuginone efficacy in improving muscle histopathology in mice with deleted dysf transmembrane domain. Quadriceps sublumbar and longissimus muscles of 9-month-old dysf-/- mice treated with halofuginone for 4 months exhibited a reduction in centrally-nucleated myofibers, inflammatory infiltrates and collagen content. Late onset of dysferlinopathy makes it ideal for evaluating the efficacy of early treatments on late outcome. The dysf-/- mice were treated with halofuginone for 3 to 4 months starting at 1, 5 or 9 months of age, and quadricep muscle histopathology was evaluated at 12 months. Collagen content and number of centrally nucleated myofibers decreased after early halofuginone treatment, administered when myofibers with central nuclei and inflammatory infiltrates are evident, but there was almost no fibrosis. When administered at the beginning of fibrosis it resulted in a further decrease in the number of centrally-nucleated myofibers with no additional decrease in collagen levels. Cardiac fibrosis was almost completely abolished following early halofuginone treatment. Halofuginone inhibited Smad3 phosphorylation and its translocation to the nucleus and increased the activity of matrix metalloproteinases 9 and 2 responsible for resolution of pre-existing collagen. Macrophage and myofibroblast invasion into the dystrophic muscle at the site of myofibers with central nuclei was inhibited by halofuginone. These results suggest that early halofuginone treatment can prevent the late outcome of dysferlinopathy and can cause resolution of the established fibrosis when administered at later stages.
Open Access
Myofibroblasts and myoepithelial cells in the chicken Harderian gland
(Murcia : F. Hernández, 1991) Cacho, Emilio del; Gallego, Margarita; Felices, Carlos; Bascuas, J.A.
An electron microscopic study of the myoepithelial cells in the chicken Harderian gland provides evidence that these cells can be transformed into myofibroblasts. After the application of a Brucella ovis suspension in sterile saline onto the eyeball, every 5 minutes for half an hour, myoepithelial cells gradually develop over a 90-minute period the characteristic features of myofibroblasts: bundles of intracytoplasmic microfilament; abundant rough endoplasmic reticulum; prominent Golgi complex; and surface membrane differentiations, that provide attachment to neighbouring epithelial cells. No typical desmosomes are observed. Besides, the intercellular space between epithelial cells and myofibroblasts increases and the basement membrane adjacent to myofibroblasts disappears. Hypoxia is hypothesized to be involved in the transformation of myoepithelial cells into myofibroblasts.
Open Access
Programmed cell death in nodular palmar fibromatosis (Morbus Dupuytren)
(Murcia : F. Hernández, 1998) Wilutzky, B.; Berndt, A.; Katenkamp, D.; Kosmehl, H.
The regular loss of cellularity during involutional phase of nodular palmar fibromatosis (Morhus D~lp~lyt r enin)d icates a regulated process known as programmed cell death (apoptosis). Using the TUNEL method apoptosis-related DNA fragmentation is detected in numerous cells as a characteristic feature of fibromatosis noduli of involutional phase. By means of double labelling technique. a-smooth muscle actin immunohistochenlistry and TUNEL method for apoptosis, i t is demonstrated that the cells which underwent apoptotosis are myofibroblasts. As anticipated, the antidote to apoptosis bcl-2 is not detected in involutional phase, but neither it is evidenced in proliferative phase. Immunohistochemically, FasIAPO-l is shown to be existent in a very small number of fibroblasts in involutional phase. However. in view of the high number of TUNEL-stained cells a significance in regulating apoptosis in nodular palmar fibromatosis seems improbable. Taking into account that the development of the fibromatosis noduli, the expression of myofibroblast phenotype, basement membrane formation and growth factor expression including TGFD culminates in involutional phase the initiation of apoptotic cell death can be discussed in relation to these growth factors and matrix protein action and the programmed cell death may be considered as the final step of myofibroblast phenotype evolution.
Open Access
Role of discoidin domain receptor 2 in wound healing
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Márquez, Joana; Olaso, Elvira
Until recently, collagen interactions with cells had been ascribed to integrins. The identification of the Discoidin Domain Receptor (DDR) family as collagen receptors represents a new paradigm in the regulation of collagen-cell interactions. How DDR signaling is biochemically linked to specific cell regulatory functions remains largely unknown. Moreover, the characteristic slow and substained phosphorylation of DDRs and the elevated expression of DDR2 in the myofibroblasts of healing wounds suggest a role for DDR2 in physiological and pathological wound healing. In fact, DDR2 signaling regulates cell proliferation and extracellular matrix synthesis, which are key aspects of fibroblast contribution to tissue healing. In this review we summarize evidence in favor of this concept.
Open Access
Significance of α-SMA in myofibroblasts emerging in renal tubulointerstitial fibrosis
(F. Hernández y Juan F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología, 2011) Ina, Keisuke; Kitamura, Hirokazu; Tatsukawa, Shuji; Fujikura, Yoshihisa
Myofibroblast transdifferentiation plays a crucial role in the development and progression of renal tubulointerstitial fibrosis. However, the significance of α-smooth muscle actin (α-SMA) expression, which is the major morphological characteristic of myofibroblasts, remains to be determined in detail. The effect of α-SMA expression on fibrosis tissue was examined by using a fibrosis model (collagen gel) in vitro. The transdifferentiation of fibroblasts into myofibroblasts was triggered in the culture medium with 0.5% fetal bovine serum (FBS)+transforming growth factor (TGF)- ß1, but not with 10% FBS+TGF-ß1. The TGF-ß1- induced gel contraction caused by myofibroblasts was greater than that by fibroblasts. Gel contraction by myofibroblasts involved the Ca2+-dependent myosin light chain kinase pathway, as well as the activation of Rho kinase and p38 mitogen-activated protein kinase (MAPK). Taken together, these findings suggest that α- SMA expression in renal interstitial fibroblasts, i.e., myofibroblast transdifferentiation, accelerates the contraction of the tubulointerstitial fibrosis tissue via the Ca2+-dependent pathway, in addition to the pathways involved in fibroblast contraction; this event may lead to renal atrophy and renal failure.
Open Access
The distribution of myofibroblasts and CD34-positive stromal cells in normal renal pelvis and ureter and their cancers
(Murcia : F. Hernández, 2006) Kuroda, Naoto; Shimasaki, N.; Miyazaki, E.; Hamauzu, T.; Toi, M.; Hiroi, Makoto; Shuin, T.; Enzan, H.
In this article, we examined the distribution of myofibroblasts and CD34-positive stromal cells in normal renal pelvis and ureter and their cancers using immunohistochemistry. Eighteen tumors and normal tissues apart from the main tumor were examined. In the wall of normal renal pelvis and ureter, no myofibroblasts were observed through all layers, but CD34-positive stromal cells were observed in the deep area of lamina propria, muscular layer and adventitia. In the stroma of renal pelvic and ureteral cancers, myofibroblasts were distributed in fifteen tumors and were absent in three tumors. All three tumors containing no myofibroblasts in the stroma were non-invasive type and all invasive cancers contained myofibroblasts in the stroma. CD34- positive stromal cells were consistently absent in the stroma of cancers, irrespective of the invasiveness. Finally, myofibroblasts are major stromal components in renal pelvic and ureteral cancers, particularly in invasive cancers, and CD34-positive stromal cells are consistently absent or lost in the stroma of their cancers. These findings suggest that the invasion of renal pelvic and ureteral cancers may cause the phenotypic change of stromal cells.
Open Access
The distribution pattern of myofibroblasts in the stroma of human bladder carcinoma depends on their invasiveness
(Murcia : F. Hernández, 2006) Shimasaki, N.; Kuroda, Naoto; Miyazaki, E.; Hayashi, Yoshihiro; Toi, M.; Hiroi, Makoto; Enzan, H.; Shuin, T.
The presence of myofibroblasts has been elucidated in the stroma of neoplasm of various organs. In the present article, we studied the distribution of myofibroblasts in the stroma of bladder carcinoma. Twenty-five surgical resected bladder tumors (urothelial carcinoma, n=21; combined urothelial carcinoma and adenocarcinoma, n=2; sarcomatoid squamous cell carcinoma, n=1; combined urothelial carcinoma and squamous cell carcinoma, n=1) were selected and we evaluated the distribution of myofibroblasts using immunohistochemical, electron and immunoelectron microscopic techniques. Immunohistochemically, the distribution pattern of myofibroblasts in invasive and non-invasive carcinomas were predominantly fascicular and reticular forms, respectively. Moreover, myofibroblasts around bladder carcinoma cells were confirmed by electron microscope. Understanding the distribution pattern of myofibroblasts in the stroma of bladder carcinoma may provide available information about the presence of carcinoma invasion.
Open Access
The fibronexus in reactive and tumoral myofibroblasts: further characterisation by electron microscopy
(Murcia : F. Hernández, 2001) Eyden, B.
Forty two surgical specimens containing myofibroblasts were studied to clarify the criteria for identifying the fibronexus, an ultrastructural feature regarded as a marker for myofibroblastic differentiation. Granulation tissue, tumour stroma, fibro-proliferative lesions (nodular fasciitis, myofibromatosis, inflammatory myofibroblastic tumour) and malignancies (myofibrosarcoma and fibrosarcoma) were studied. Comparable results were found throughout these specimens, although fibronexus junctions were better developed in reactive compared with tumoral myofibroblasts. By electron microscopy, myofibroblasts were identified by abundant rough endoplasmic reticulum, peripheral smooth-muscle myofilaments with foca1 densities, and fibronexus junctions. The latter were recognised as the points of convergence on the myofibroblast surfaces of intracellular myofilaments and extracellular fibronectin fibrils. The fibronectin fibrils were often co-linear with myofilaments. Also, fibronectin fibrils were dark-staining, straight and rigidlooking, and had a longitudinal filamentous substructure. A striking feature was the tendency of fibronectin fibrils to project into the surrounding extracellular space, away from the myofibroblast surface: in these respects, they differed significantly from lamina ("basement membrane"). The presence of fibronectin fibrils correlated positively with fibronectin immunostaining by light and electron microscopy. Laminin and collagen IV showed variable and weak staining in the intercellular spaces in a minority of cases and never strongly stained myofibroblast surfaces. The data emphasise that the fibronexus has a number of distinctive features permitting identification, and constitute a reference-point for pathologists wishing to use electron microscopy to refine light microscopy diagnoses of putative myofibroblastic lesions. The role of the fibronexus in the definition of the myofibroblast is discussed.
Open Access
The participation of myofibroblasts in the capsular formation of human conventional and chromophobe renal cell carcinomas
(Murcia : F. Hernández, 2005) Shimasaki, N.; Kuroda, Naoto; Guo, L.; Jin, Y.; Miyazaki, E.; Hayashi, Yoshihiro; Toi, M.; Hiroi, Makoto; Enzan, H.; Shuin, T.
The presence of myofibroblasts has been elucidated in neoplastic capsules of various organs. In the present article, we examine the presence of myofibroblasts in the capsule of renal cell carcinoma (RCC) and discuss the origin of the myofibroblasts. Nineteen renal tumors (conventional RCC, n=17; chromophobe RCC, n=2) with evident and totally surrounded fibrous capsule were selected. Abundant myofibroblasts were immunohistochemically observed in the capsule of the RCCs. These findings were confirmed by electron and immunoelectron microscopic studies of three conventional RCCs. Type III and I collagens were predominant in the outer and inner layers of the RCC capsule, respectively. The cytoplasm of the tubular epithelial cells in the tissue surrounding the neoplastic capsule stained positively for transforming growth factor (TGF)-ß1. In situ hybridization detected type I collagen mRNA in myofibroblasts of the capsule. Myofibroblasts may participate in the capsular formation of conventional and chromophobe RCCs through the collagen production.
Open Access
Tumor-associated fibroblasts (Part I): active stromal participants in tumor development and progression?
(Murcia: F. Hernández, 2002) Kunz-Schughart, L.A.; Knuechel, R.
Phenotypic and functional characteristics of tumor associated fibroblasts (TAF) in contrast to normal fibroblasts are re v i e wed in this first synopsis (part I). Terms as tumor stroma, desmo-plasia, T A F , myofibroblast, and fetal-type fibroblast are defined, and experimental systems to study heterologous cell interactions are presented. While we only start to gather information on the genotype of T A F , a broad range of data deals with the e xpression profile of these cells, co v ering e.g. ECM and ECM-modulating molecules, growth factors and cytokines. Summarizing the recent state of kno w l e d g e indicates that TAF provide sources for tumor diagnosis and therap y , that ha v e to be further defined in an or g an- s p e c i f ic approach in terms of the functional impact on the tumor cell and its environment (see part II).

Browsing by Subject "Myofibroblast"

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