Leptin augments myofibroblastic conversion and fibrogenic activity of human peritoneal mesothelial cells: a functional implication for peritoneal fibrosis.

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.