Leptin augments myofibroblastic conversion and fibrogenic activity of human peritoneal mesothelial cells: a functional implication for peritoneal fibrosis. |
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Authors: | An-Hang Yang Seng-Wong Huang Jin-Yang Chen Jan-Kou Lin Chun-Yi Chen |
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Institution: | Division of Ultrastructural and Molecular Pathology, Department of Pathology, Taipei Veterans General Hospital, Taipei 112, Taiwan. ahyang@vghtpe.gov.tw |
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Abstract: | BACKGROUND: Myofibroblastic conversion of mesothelial cells is proposed to play an important role in pathological changes following serosal membrane injury. METHODS: Human peritoneal mesothelial cells (HPMCs) were isolated and maintained in culture. The gene expression was assessed by RT-PCR. Activation of signal transduction was determined by western blot and densitometry. Morphological changes were observed by phase-contrast and electron microscopy. RESULTS: In vitro study showed that TGF-beta1-induced myofibroblastic growth of HPMCs was significantly enhanced in the presence of leptin. Augmented expression of alpha-smooth muscle actin, fibronectin and type I collagen mRNA in HPMCs induced by leptin were TGF-beta1-dependent, suggesting that leptin promoted peritoneal fibrogenesis through synergistic activation of the TGF-beta1 signaling system. Leptin and TGF-beta1 synergistically augmented activation of signalling components of mitogen-activated protein kinase (MAPK), STAT3 and Smad but did not modulate the expression of LEPR-B. CONCLUSION: Leptin may act as a profibrogenic TGF-beta1 activated cytokine in peritoneal bioenvironment associated with TGF-beta1 activated pathogenic processes. |
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Keywords: | dialysis fibrosis leptin mesothelial cell myofibroblast TGF-ß 1 |
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