title: Inhibitory effect of l-mimosine on bleomycin-induced pulmonary fibrosis in rats: Role of eIF3a and p27.
abstract: It has also been shown that the decreased expression of eukaryotic translation initiation factor 3a (eIF3a) by L-mimosine caused cell cycle arrest. Our previous study has found that eIF3a is involved in bleomycin-induced pulmonary fibrosis. Whether the eIF3a/p27 signal pathway is involved in the inhibitory effect of L-mimosine on bleomycin-induced pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of eIF3a, p27, α-SMA, collagen I and collagen III was analyzed by qPCR and Western blot. In vivo, L-mimosine treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of eIF3a, α-SMA, collagen I and collagen III (both mRNA and protein) and expression down- regulation of p27. In vitro, L-mimosine remarkably attenuated proliferation of pulmonary fibroblasts and expression of α-SMA, collagen I and collagen III induced by TGF-β1, and this inhibitory effect of L-mimosine was accompanied by inhibiting eIF3a expression and increasing p27 expression. Knockdown of eIF3a gene expression reversed TGF-β1-induced proliferation of fibroblasts, down-regulation of p27 expression and up-regulation of α-SMA, collagen I, and collagen III expression. These results suggest that L-mimosine inhibited the progression of bleomycin-induced pulmonary fibrosis in rats via the eIF3a/p27 pathway.
authors.affiliation: Department of Pharmacology, Wannan Medical College, Wuhu 241002, Anhui, 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. Electronic address: huchangping@yahoo.com.
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.
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Immunology, Wannan Medical College, Wuhu 241002, China.
authors.forename: Yuan-Xing
authors.initials: YX
authors.lastname: Gao
authors.affiliation: Department of Pathology, Wannan Medical College, Wuhu 241002, China.
authors.forename: Xiang-Ming
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Wannan Medical College, Wuhu 241002, Anhui, China.
authors.forename: Jie-Ren
authors.initials: JR
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000473:pathology*; D008297:Male; D008898:Mimosine / Q000008:administration & dosage* / Q000009:adverse effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D039621:Eukaryotic Initiation Factor-3; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008898:Mimosine; D003094:Collagen
keywords: Eukaryotic translation initiation factor 3a; Pulmonary fibroblasts; Pulmonary fibrosis; l-Mimosine; p27