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.
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.
Authors: Jesús Loureiro; Pilar Sandoval; Gloria del Peso; Guadalupe Gónzalez-Mateo; Vanessa Fernández-Millara; Beatríz Santamaria; Maria Auxiliadora Bajo; José Antonio Sánchez-Tomero; Gonzalo Guerra-Azcona; Rafael Selgas; Manuel López-Cabrera; Abelardo I Aguilera Journal: PLoS One Date: 2013-04-23 Impact factor: 3.240