title: PPAR-γ inhibits IL-13-induced collagen production in mouse airway fibroblasts.
abstract: Interleukin-13 (IL-13) plays an important role in extracellular matrix production of airway remodeling in asthma. Activation of PPAR-γ has been shown to inhibit the occurrence of airway fibrosis in asthma, yet it remains unknown whether the effect of PPAR-γ on suppression of airway fibrosis is associated with the inhibition of IL-13 signaling. In the present study, primary cultured airway fibroblasts were stimulated with IL-13, and JAK inhibitor, PDGF receptor blocker and MEK inhibitor were applied to investigate the involvement of these pathways in IL-13-induced collagen production. Our results demonstrate that IL-13 dose- and time-dependently induced collagen production in primary cultured mouse airway fibroblasts; this effect was blocked by inhibition of JAK/STAT6 signal pathway. IL-13 also stimulated JAK/STAT6-dependent PDGF production, elevation of PDGF in turn activated ERK1/2 MAPK and caused collagen production. Activation of PPAR-γ by rosiglitazone reduced IL-13-induced collagen expression by suppression of STAT6-driven PDGF production. Our results indicate that activation of JAK/STAT6 signal and subsequent PDGF generation and ERK1/2 MAPK activation mediate IL-13-induced collagen production in airway fibroblasts. This study suggests that activation of PPAR-γ might be a novel strategy for the treatment of asthma partially by inhibition of airway fibrosis.
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Lu
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Guizuo
authors.initials: G
authors.lastname: Wang
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Xinming
authors.initials: X
authors.lastname: Xie
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ke
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Shaojun
authors.initials: S
authors.lastname: Li
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Xie
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Fang
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Sun
authors.affiliation: Respiratory Diseases Research Center, Xi׳an Jiaotong University, Shaanxi, Xi׳an 710004, PR China; Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi׳an Jiaotong University, No. 157, West 5th Road, Shaanxi, Xi׳an 710004, PR China. Electronic address: manxiangli@hotmail.com.
authors.forename: Manxiang
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D003094:Collagen / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D018793:Interleukin-13 / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D012137:Respiratory System / Q000166:cytology*; D000077154:Rosiglitazone; D050800:STAT6 Transcription Factor / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D018793:Interleukin-13; D047495:PPAR gamma; D010982:Platelet-Derived Growth Factor; D050800:STAT6 Transcription Factor; D045162:Thiazolidinediones; C075278:platelet-derived growth factor A; D000077154:Rosiglitazone; D003094:Collagen; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: PPAR-γ (PubChem CID: 77999)