Prevention of bleomycin-induced pulmonary fibrosis by a RANKL peptide in mice

• DOI: 10.1038/s41598-022-16843-7
• Publication Date: 2022-07-21T17:03:05Z
• Authors: Nan Ju; Hiroki Hayashi; Munehisa Shimamura; Satoshi Baba; Shota Yoshida; Ryuichi Morishita; Hiromi Rakugi; Hironori Nakagami
• Keywords: Proinflammatory cytokine

Abstract Despite the recent therapeutic developments for treatment of pulmonary fibrosis, its prognosis is still not well controlled, and a novel agent needed. Recently, critical role Toll-like receptors (TLRs) in pathophysiology fibrosis has been reported; however, effects multiple TLR signaling inhibition are unknown. Here, we examined how TLRs affects using synthetic receptor activator nuclear factor κB ligand (RANKL) partial peptide, MHP1-AcN, which could suppress TLR2, 3, 4, 7, 9 through CD14 RANK. When MHP1-AcN was administered bleomycin-induced lung model, reduced collagen deposition observed, with suppressed fibrosis-related gene expression including Col1a1 , Col1a2 Acta2 Tgfb1 Tgfbr2 . also decreased proinflammatory M1 profibrotic M2 macrophage marker expression. Furthermore, inhibited transforming growth (TGF-β)-induced Smad2/3 phosphorylation myofibroblast differentiation human fetal fibroblast (MRC-5) cells. This effect associated TGF-β levels upregulated Bmp7 Smad7 These findings suggest that protects mice against fibrosis. might provide strategy