title: Aberrant TGF-β1 signaling contributes to the development of primary biliary cirrhosis in murine model.
abstract: OBJECTIVE
  To investigate whether transforming growth factor-β1 (TGF-β1) signaling pathway is involved in the pathogenesis of primary biliary cirrhosis (PBC).
  
  
  METHODS
  A murine model of PBC was developed by injection of polyinosinic polycytidylic acids (poly I: C) in C57BL/6 mice, and the liver expressions of TGF β1, TGF-β receptor I (TβRI), TGF-β receptor II (TβRII), p-Smad2/3, monoclonal α-smooth muscle actin antibody (α-SMA) and α1 (I) collagen in the mouse model and control mice were evaluated by immunohistochemistry, immunoblotting and real-time polymerase chain reaction (RT-PCR). Lymphocyte subsets in liver were analyzed using flow cytometry.
  
  
  RESULTS
  The mouse model had several key phenotypic features of human PBC, including elevated levels of alkaline phosphatase, antimitochondrial antibodies, portal bile ducts inflammation, and progressive collagen deposition. Compared with control mice, protein and mRNA levels of TGF β1, TβRI, TβRII, p-Smad2/3, α-SMA and α1 (I) collagen in liver (1.7 ± 0.4 vs 8.9 ± 1.8, 0.8 ± 0.2 vs 5.1 ± 1.5, 0.6 ± 0.01 vs 5.1 ± 0.1, 0.6 ± 0.3 vs 2.0 ± 0.3, 0.9 ± 0.4 vs 3.4 ± 0.6, 0.8 ± 0.4 vs 1.7 ± 0.3, 1.1 ± 1.2 vs 11.8 ± 0.6, P < 0.05), and the total number and percentage of CD4⁺ CD25⁺ FOXP3⁺ and CD8⁺ lymphocytes (0.01 ± 0.001 vs 0.004 ± 0.00, 0.12 ± 0.04 vs 0.52 ± 0.23, P < 0.01) were higher in the mouse model.
  
  
  CONCLUSIONS
  TGFβ1 might play a dual role in the development of PBC: it suppresses inflammatory response but operates to enhance fibrogenesis. The aberrant activity of TGF-β1 signaling contributes to the development of PBC.
authors.affiliation: Bin Liu, Jin-Bao Zong, Department of Rheumatology, the Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, Shandong Province, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Feng-Chun
authors.initials: FC
authors.lastname: Zhang
authors.forename: Jin-Bao
authors.initials: JB
authors.lastname: Zong
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011070:Poly I-C; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011070:Poly I-C
keywords: Liver; Primary biliary cirrhosis; Regulatory T cell; Transforming growth factor-β1