title: Nuclear factor (NF)-κB p65 regulates differentiation of human and mouse lung fibroblasts mediated by TGF-β.
abstract: OBJECTIVE
  Nuclear factor (NF)-κB signaling pathway contributes to the pathogenesis of lung fibrosis. However, the expression and roles of NF-κB p65 subunit in fibroblasts under fibrotic conditions have not been studied. We checked the expression of p65 in lung tissue and fibroblasts from bleomycin (BLM) challenged mice and investigated the roles of p65 in human lung fibroblast differentiation during transforming growth factor β (TGF-β) challenge.
  
  
  METHODS
  A murine model of BLM-induced lung fibrosis and in vitro cultures of lung fibroblast from human and mouse were used to study the expression and role of p65 during fibrogenesis. The si-RNA knockdown strategy was used to check the mechanism of TGF-β induced p65 expression and roles of p65 during fibroblast differentiation.
  
  
  RESULTS
  We found that the expression of p65 was significantly increased in lung tissue, fibrotic foci and fibroblast from BLM-challenged mice. In vitro, TGF-β stimulated p65 expression, nuclear translocation and cell differentiation in human lung fibroblast; knockdown smad3 expression inhibited TGF-β-induced p65 expression and differentiation in human lung fibroblast. Additionally, knockdown the expression of p65 suppressed TGF-β-induced differentiation and p65 translocation to nuclei in human lung fibroblast.
  
  
  CONCLUSIONS
  These data suggested that p65 expression is up-regulated in lung fibroblast during differentiation through TGF-β/smad3 pathway and synergistically regulates TGF-β induced differentiation of lung fibroblasts.
authors.affiliation: School of Stomatology, Capital Medical University, No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China; Department of Pediatrics, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Sun
authors.affiliation: Beijing Tongren Hospital, Capital Medical University, No. 8 Chongwenmennei Street, Dongcheng District, Beijing 100005, China.
authors.forename: Erjun
authors.initials: E
authors.lastname: Chen
authors.affiliation: School of Stomatology, Capital Medical University, No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Dong
authors.affiliation: The Center of Translational Research Shanghai Tenth People's Hospital, Tongji University, Shanghai 200092, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Chen
authors.affiliation: School of Stomatology, Capital Medical University, No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China. Electronic address: shuaiyu369@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001761:Bleomycin / Q000633:toxicity; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008168:Lung / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D000903:Antibiotics, Antineoplastic; D051900:Smad3 Protein; D051996:Transcription Factor RelA; D016212:Transforming Growth Factor beta; D001761:Bleomycin
keywords: Fibroblast; Pulmonary fibrosis; TGF-β; p65