title: Calcitonin gene-related peptide down-regulates bleomycin-induced pulmonary fibrosis.
abstract: We have found that eIF3a plays an important role in bleomycin-induced pulmonary fibrosis, and up-regulation of eIF3a induced by TGF-β1 is mediated via the ERK1/2 pathway. Whether ERK1/2 - eIF3a signal pathway is involved in calcitonin gene-related peptide (CGRP)-mediated pathogenesis of 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. Sensory CGRP depletion by capsaicin exacerbated bleomycin-induced pulmonary fibrosis in rats, as shown by a significant disturbed alveolar structure, marked thickening of the interalveolar septa and dense interstitial infiltration by inflammatory cells and fibroblasts, accompanied with increased expression of TGF-β1, eIF3a, phosphorylated ERK1/2, α-SMA, collagen I, and collagen III. Exogenous application of CGRP significantly inhibited TGF-β1-induced proliferation and differentiation of pulmonary fibroblasts concomitantly with decreased expression of eIF3a, phosphorylated ERK1/2, α-SMA, collagen I, and collagen III. These effects of CGRP were abolished in the presence of CGRP8-37. These results suggest that endogenous CGRP is related to the development of pulmonary fibrosis induced by bleomycin, and the inhibitory effect of CGRP on proliferation of lung fibroblasts involves the ERK1/2 - eIF3a signaling pathway.
authors.affiliation: a Department of Pharmacology, Wannan Medical College, Wen-Chang West Road #22, Wuhu, Anhui 241002, China.
authors.forename: Xian-Wei
authors.initials: XW
authors.lastname: Li
authors.affiliation: b Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road #110, Changsha, Hunan 410078, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Li
authors.affiliation: b Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road #110, Changsha, Hunan 410078, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.affiliation: b Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road #110, Changsha, Hunan 410078, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Li
authors.affiliation: b Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road #110, Changsha, Hunan 410078, China.
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
authors.affiliation: b Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road #110, Changsha, Hunan 410078, China.
authors.forename: Chang-Ping
authors.initials: CP
authors.lastname: Hu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001761:Bleomycin / Q000633:toxicity*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D015740:Calcitonin Gene-Related Peptide
keywords: TGF-β1; calcitonin gene-related peptide; eukaryotic translation initiation factor 3a; facteur 3a de démarrage de la traduction eucaryote; fibroblastes pulmonaires; fibrose pulmonaire; peptide lié au gène de la calcitonine; pulmonary fibroblasts; pulmonary fibrosis