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: Xian-Wei Li, Chang-Ping Hu, Yuan-Jian Li, Yuan-Xing Gao, Xiang-Ming Wang, Jie-Ren Yang
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 27 Issue 1 Pg. 53-64 (Jul 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 25957199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier B.V.

Chemical References

• ACTA2 protein, human
• Actins
• Eukaryotic Initiation Factor-3
• RNA, Small Interfering
• Transforming Growth Factor beta
• Bleomycin
• Cyclin-Dependent Kinase Inhibitor p27
• Mimosine
• Collagen

Topics

• Actins (genetics, metabolism)
• Animals
• Bleomycin (administration & dosage)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Collagen (metabolism)
• Cyclin-Dependent Kinase Inhibitor p27 (genetics, metabolism)
• Eukaryotic Initiation Factor-3 (genetics, metabolism)
• Fibroblasts (drug effects, physiology)
• Gene Expression Regulation (drug effects)
• Humans
• Lung (pathology)
• Male
• Mimosine (administration & dosage, adverse effects)
• Pulmonary Fibrosis (chemically induced, drug therapy)
• RNA, Small Interfering (genetics)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Transforming Growth Factor beta (metabolism)