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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / genetics
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Actins / metabolism
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Blotting, Western
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Cells, Cultured
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Collagen Type I / genetics
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Collagen Type I / metabolism
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Enzyme Activation
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Epithelium / drug effects
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Epithelium / ultrastructure*
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Fibronectins / genetics
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Fibronectins / metabolism
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Fibrosis / genetics
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Fibrosis / pathology
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Gene Expression
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Humans
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Leptin / pharmacology
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Microscopy, Electron
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / metabolism
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Peritoneum / drug effects
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Peritoneum / pathology*
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RNA, Messenger / genetics
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Receptors, Leptin
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Reverse Transcriptase Polymerase Chain Reaction
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism
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Smad2 Protein / genetics
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Smad2 Protein / metabolism
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Smad3 Protein / genetics
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Smad3 Protein / metabolism
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Transforming Growth Factor beta1 / metabolism
Substances
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Actins
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Collagen Type I
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Fibronectins
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LEPR protein, human
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Leptin
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RNA, Messenger
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Receptors, Cell Surface
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Receptors, Leptin
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STAT3 Transcription Factor
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STAT3 protein, human
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Smad2 Protein
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Smad3 Protein
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Transforming Growth Factor beta1
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3