title: Bone Marrow Stromal Cells Inhibit the Activation of Liver Cirrhotic Fat-Storing Cells via Adrenomedullin Secretion.
abstract: BACKGROUND
  Cirrhosis, or liver fibrosis, which is mainly triggered by cirrhosis fat-storing cells (CFSCs) activation, has traditionally been considered an irreversible disease. However, recent observations indicate that even advanced fibrosis is still reversible by removing the causative agents. Anti-fibrotic effects of bone marrow-derived stromal cells (BMSCs) have been demonstrated by inhibiting CFSCs via cytokines secretion; however, the mechanisms are still unclear.
  
  
  OBJECTIVE
  The purpose of this study was to explore the underlying mechanisms by which BMSCs modulate the function of activated CFSCs.
  
  
  METHODS
  After the co-culture of CFSCs with BMSCs supernatants with or without the addition of recombinant rat adrenomedullin (AM)/AM-specific siRNA, western blot analysis was mainly used to detect the differences of relative protein expression on CFSCs.
  
  
  RESULTS
  BMSC-secreted adrenomedullin (AM) effectively inhibited the proliferation and activation of CFSCs by suppressing the expression of Ang II and its binding receptor, AT1, which resulted in a reduction of p47-phox formation.
  
  
  CONCLUSIONS
  Our data suggested that BMSCs inhibited CFSC activation in vitro via the AM-Ang II-p47-phox signaling pathway, and since CFSC activation is an essential part of hepatic fibrosis process, this inhibition by BMSCs implies us new insights into the potential treatment of hepatic fibrosis via BMSCs.
authors.affiliation: Emergency Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Bao Jian Road, Nangang District, Harbin, 150086, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Jinghua
authors.initials: J
authors.lastname: Wang
authors.forename: Kexin
authors.initials: K
authors.lastname: Shi
authors.forename: Xufu
authors.initials: X
authors.lastname: Qin
authors.forename: Qingfei
authors.initials: Q
authors.lastname: Kong
authors.forename: Guangyou
authors.initials: G
authors.lastname: Wang
authors.forename: Lili
authors.initials: L
authors.lastname: Mu
authors.forename: Hulun
authors.initials: H
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.forename: Lijun
authors.initials: L
authors.lastname: Shi
mesh_terms: D000199:Actins / Q000378:metabolism; D053607:Adrenomedullin / Q000235:genetics / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D024042:Collagen Type I / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D019899:Paracrine Communication; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014162:Transfection
chemical_list: D000199:Actins; D053607:Adrenomedullin; D000804:Angiotensin II; D024042:Collagen Type I; D019255:NADPH Oxidases; D044140:Receptor, Angiotensin, Type 1; D020797:Receptor, Platelet-Derived Growth Factor beta; D019715:Tissue Inhibitor of Metalloproteinase-1; C576839:TIMP1 protein, rat; C498862:Acta2 protein, rat; C060505:neutrophil cytosolic factor 1