title: Angiotensin-(1-7) decreases the expression of collagen I via TGF-β1/Smad2/3 and subsequently inhibits fibroblast-myofibroblast transition.
abstract: Previous studies have shown that the RAS (renin-angiotensin system) might participate in airway remodelling in asthma. As a main component of the RAS, Ang-(1-7) [angiotensin-(1-7)] has been reported in few studies regarding its protective effect on asthma. However, the functional roles and relevant signalling pathways of Ang-(1-7) have not been well illustrated. In the present study, we analysed the effect of Ang-(1-7) on AngII (angiotensin II)-induced HLF (human lung fibroblast)-MF (myofibroblast) transition by detecting Col-I (collagen type I), TGF-β1 (transforming growth factor-β1) and α-SMA (α-smooth muscle actin) expression. We explored further the possible signalling pathways involved in HLF-MF transition. Our results showed that Ang-(1-7) could down-regulate the expression of Col-I, α-SMA and TGF-β1/Smad2/3 (all P<0.05). A significant decrease was found in phosphorylation of PI3K (phosphoinositide 3-kinase), Akt, p38-MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase) signalling pathways during HLF-MF transition (all P<0.05). Our data suggests that Ang-(1-7) decreases the expression of Col-I via TGF-β1/Smad2/3 and subsequently inhibits HLF-MF transition.
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jian Ping
authors.initials: JP
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Chen Juan
authors.initials: CJ
authors.lastname: Gu
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China liqingyun68@hotmail.com.
authors.forename: Qing Yun
authors.initials: QY
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Huan Ying
authors.initials: HY
authors.lastname: Wan
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000803:Angiotensin I / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D058628:Myofibroblasts / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D024042:Collagen Type I; D010446:Peptide Fragments; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D000803:Angiotensin I; D019869:Phosphatidylinositol 3-Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C118790:angiotensin I (1-7)
keywords: Smad2/3; TGF-β1; airway remodelling; angiotensin-(1–7); collagen-I; human lung fibroblast–myofibroblast transition