title: Leptin augments myofibroblastic conversion and fibrogenic activity of human peritoneal mesothelial cells: a functional implication for peritoneal fibrosis.
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.
  
  
  CONCLUSIONS
  Leptin may act as a profibrogenic TGF-beta1 activated cytokine in peritoneal bioenvironment associated with TGF-beta1 activated pathogenic processes.
authors.affiliation: Division of Ultrastructural and Molecular Pathology, Department of Pathology, Taipei Veterans General Hospital, Taipei 112, Taiwan. ahyang@vghtpe.gov.tw
authors.forename: An-Hang
authors.initials: AH
authors.lastname: Yang
authors.forename: Seng-Wong
authors.initials: SW
authors.lastname: Huang
authors.forename: Jin-Yang
authors.initials: JY
authors.lastname: Chen
authors.forename: Jan-Kou
authors.initials: JK
authors.lastname: Lin
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D004848:Epithelium / Q000187:drug effects / Q000648:ultrastructure*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D020738:Leptin / Q000494:pharmacology; D008854:Microscopy, Electron; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D024042:Collagen Type I; D005353:Fibronectins; C515448:LEPR protein, human; D020738:Leptin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3