RRC ID 72128
著者 Ju N, Hayashi H, Shimamura M, Baba S, Yoshida S, Morishita R, Rakugi H, Nakagami H.
タイトル Prevention of bleomycin-induced pulmonary fibrosis by a RANKL peptide in mice.
ジャーナル Sci Rep
Abstract Despite the recent therapeutic developments for the treatment of pulmonary fibrosis, its prognosis is still not well controlled, and a novel therapeutic agent is needed. Recently, the critical role of Toll-like receptors (TLRs) in the pathophysiology of pulmonary fibrosis has been reported; however, the effects of multiple TLR signaling inhibition are still unknown. Here, we examined how the inhibition of multiple TLRs affects pulmonary fibrosis using a novel synthetic receptor activator of nuclear factor κB ligand (RANKL) partial peptide, MHP1-AcN, which could suppress TLR2, 3, 4, 7, and 9 signaling through CD14 and RANK. When MHP1-AcN was administered in the bleomycin-induced lung fibrosis model, reduced collagen deposition was observed, with suppressed fibrosis-related gene expression including Col1a1, Col1a2, Acta2, Tgfb1 and Tgfbr2. MHP1-AcN also decreased proinflammatory M1 and profibrotic M2 macrophage marker expression. Furthermore, MHP1-AcN treatment inhibited transforming growth factor (TGF-β)-induced Smad2/3 phosphorylation and myofibroblast differentiation in human fetal lung fibroblast (MRC-5) cells. This effect was associated with decreased TGF-β receptor levels and the upregulated Bmp7 and Smad7 expression. These findings suggest that MHP1-AcN protects mice against bleomycin-induced pulmonary fibrosis. MHP1-AcN might provide a novel therapeutic strategy for the pulmonary fibrosis.
巻・号 12(1)
ページ 12474
公開日 2022-7-21
DOI 10.1038/s41598-022-16843-7
PII 10.1038/s41598-022-16843-7
PMID 35864207
PMC PMC9304352
MeSH Animals Bleomycin / metabolism Bleomycin / toxicity Fibroblasts / metabolism Humans Lung / pathology Mice Mice, Inbred C57BL Peptides / metabolism Pulmonary Fibrosis* / chemically induced Pulmonary Fibrosis* / metabolism Pulmonary Fibrosis* / prevention & control RANK Ligand / metabolism Transforming Growth Factor beta / metabolism
IF 3.998
リソース情報
ヒト・動物細胞 MRC-5(RCB0218)