TGF- ß1 and Integrin Promote Rat Podocytes with Phenotypic Change of Positive α-Smooth Muscle Actin in Vitro

變形生長因子-ß1和結合素促進老鼠腎絲球足細胞轉分化成肌纖維母細胞

陳建安(Chain-Ann Chen) ； 陳鴻鈞(Hung-Chun Chen) ； 蘇炳文(Ping-Wen Su) ； 林建任(Jiann-Renn Li) ； 黃志強 ； 賴永勳(Yung-Hsiung Lai)

《Acta Nephrologica》 14卷4期 (2000/10) Pp. 286-286

並列摘要

The formation of focal segmental glomerulosclerosis (FSGS) is a common pathway of progressive glomerular diseases. The podocyte loss and naked glomerular capillary loop adhesion to Bowman’s capsule with sclerosis (synechiae) are the early appearance and nidus of FSGS. The glomerular basement membrane is thickened, wrinkled, then collapsed and sclerosis. The sclerotic lesions are consisted of, in addition to the increased expression of extracellular matrix (ECM) components normally observed in glomeruli, altered components of ECM are also included, appearing as the expression of collagens I and III. The collagen I and III are interstitial collagens that are synthesized by interstitial myofibroblasts and not found in normal GBM. Some authors have postulated that interstitial myofibroblasts may also contribute to glomerulosclerosis by their infiltration of Bowman’s space and glomeruli through breaks in Bowman’s capsule. But recently, podocyte bridages between the tuft and Bowman’s capsule is found at experimental crescenic glomerulonephrtis. Those podocyte bridages were interposed between parietal epithelial cell and later between the cells of a crescent. The collagen type I and α-smooth muscle actin (α-SMA)+myofibroblasts were found in the development of fibrous crescents. The podcytes were found to undergo phenotypic changes and expression macrophagic-associated markers in idiopatic collapsing glomerulopathy. The podocyte transdifferentiation was also found in posttransplantation relapse of FSGS. So, the increased and altered ECM production may be contribution from podocyte with phenotypic change.
The role of transforming growth factor-ß (TGF- ß) in the development of glomerulosclerosis has been established in experimental glomerular diseased and in African American end-stage renal disease patients. TGF- ß regulated many aspects of cellular function, including proliferation, adhesion, integrin regulation, migration, protease activity, ECM formation and phenotypic change. TGF- ß is involved in epithelial-mesenchymal transformation and myofibroblast transdifferentiation from fibroblast, mesangial cell and tubular epithelial cell.
The integrin ß 1 is the major surface ligand of podocyte with ECM. The interconnection may regulate cell functions, such as growth and migration, differentiation and gene expression, and ECM remodeling. The integrin ß 1 was found to implicate in mesenchymal-epithelial transformation.
Our present study was performed to know that podocyte where or not can be undergo phenotypic change of myofibroblast-like (α-SMA+) influenced by TGF- ß 1 and integrin to further understand the mechanism of progressive renal disease.