title: Role of eukaryotic translation initiation factor 3a in bleomycin-induced pulmonary fibrosis.
abstract: Eukaryotic translation initiation factor 3a (eIF3a) is a multifunctional protein and plays an important role in regulation of cellular function including proliferation and differentiation. In the present study, we tested the function of eIF3a in pulmonary fibrosis. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5mg/kg) in rats. Primary pulmonary fibroblasts were cultured for proliferation investigation by BrdU incorporation method and flow cytometry. The expression/level of eIF3a, TGF-β1, ERK1/2 and α-SMA were analyzed by ELISA, real-time PCR or western blot. Results showed that the expression of eIF3a was obviously increased in lungs of pulmonary fibrosis rats accompanied by up-regulation of α-SMA and collagens. In cultured pulmonary fibroblasts, application of exogenous TGF-β1 induced cell proliferation and differentiation concomitantly with up-regulation of eIF3a expression and ERK1/2 phosphorylation. The effects of TGF-β1-induced proliferation of fibroblasts and up-regulation of α-SMA were abolished by eIF3a siRNA. TGF-β1-induced eIF3a expression was reversed in the presence of PD98059, an inhibitor of ERK1/2. These findings suggest that eIF3a plays an important role in bleomycin-induced pulmonary fibrosis by regulating pulmonary fibroblasts׳ function, and up-regulation of eIF3a induced by TGF-β1 is mediated via the ERK1/2 pathway.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China; Department of Pharmacology, Wannan Medical College, Wuhu 241002, China.
authors.forename: Xian-Wei
authors.initials: XW
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Yue-Han
authors.initials: YH
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Li
authors.affiliation: National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha 410078, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Chang-Ping
authors.initials: CP
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China. Electronic address: yuan_jianli@yahoo.com.
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects*; D003094:Collagen / Q000378:metabolism; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D039621:Eukaryotic Initiation Factor-3; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D003094:Collagen
keywords: ERK1/2; Eukaryotic translation initiation factor 3a; Pulmonary fibroblasts; Pulmonary fibrosis; TGF-β(1)