Heterogeneity of Macrophage Populations and Myofibroblasts Appearing in Rat Renal Interstitial Fibrosis
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概要
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Macrophages and myofibroblasts play important roles in progressive renal fibrosis. Using cisplatin-induced rat renal fibrosis models, the author has investigated patho-biological characteristics of these cells. Macrophages seen in the fibrotic areas involve exudate macrophages, resident macrophages and antigen-presenting cells (activated dendritic cells and macrophages). In the early stages of renal fibrosis, exudate and resident macrophages are key cells for induction of myofibroblasts via producing fibrogenic factors such as transforming growth factor (TGF)-β1 and platelet-derived growth factor (PDGF)-BB. In addition, these macrophages have capacity to phagocytize apoptotic bodies for clearance. The antigen-presenting cells are responsible for immune-mediated T-cell induction and subsequent B cell proliferation in the advanced stages. Myofibroblasts show various cytoskeletons (vimentin, α-smooth muscle actin (SMA), and desmin) during the development. In severely-developed fibrotic lesions, both renal epithelia and interstitial cells give immuno-positive reactions to α-SMA and vimentin, supporting epithelial-mesenchymal transition (EMT) in which renal epithelial cells acquire myofibroblastic nature. Desmin is expressed in interstitial cells, but not in renal epithelia. In vitro exposure of TGF-β1 to porcine renal epithelial cells (LLC-PK1), rat renal interstitial fibroblastic cells (NRK-49F), and rat pluripotential mesenchymal cells (MT-9; pericytes) increase the α-SMA-positive myofibroblastic cell number. PDGF-BB has an additive effect on TGF-β1-induced α-SMA expression in these cell lines. Collectively, different macrophage populations participate in progressive renal fibrosis, and precursors of myofibroblasts are heterogeneous (renal epithelial cells undergoing EMA, interstitial fibroblasts and immature mesenchymal cells). The regulation of macrophages and myofibroblast development would provide therapeutic strategies in clinical trials of progressive renal fibrosis.
- 日本毒性病理学会の論文
- 2007-12-25
著者
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Yamate Jyoji
Laboratory Of Veterinary Pathology Life And Environmental Sciences Osaka Prefecture University
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Yamate Jyoji
Laboratory Of Veterinary Pathology Division Of Veterinary Sciences Graduate School Of Life And Environmental Sciences Osaka Prefecture University
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