Peptide PD29 treats bleomycin-induced pulmonary fibrosis by inhibiting the TGF-β/smad signaling pathway. (3rd July 2019)

• Record Type: Journal Article
• Authors: Sun, Qingbo; Hu, Jialiang; Yu, Pengcheng; Zhu, Zhaohao; Yu, Ruihe; Ge, Chuang; Li, Chencheng; Wu, Guiyue; Lin, Bingjing; Liu, Guangpan; Liu, Meng; Bian, Huan; Xu, Hanmei; Jia, Shaochang
• Is Part Of: Experimental lung research. Volume 45:Number 5/6(2019)
• Page Start: 123
• Page End: 134
• Publication Date: 2019-07-03
• Subjects: Pulmonary fibrosis -- PD29 -- EMT -- TGF-β1/Smad2/3 signaling pathway; Lungs -- Periodicals; Lungs -- Diseases -- Periodicals; Lung Diseases; Lung -- physiology; Respiratory System; 616.24
• DOI: 10.1080/01902148.2019.1614696
• Languages: English
• ISSNs: 0190-2148

Abstract

Abstract: Pulmonary fibrosis (PF) is an end-stage change in lung disease characterized by fibroblast proliferation, massive extracellular matrix (ECM) aggregation with inflammatory damage, and severe structural deterioration. PD29 is a 29-amino acid peptide which has the potential to alleviate PF pathogenesis via three mechanisms: anti-angiogenesis, inhibition of matrix metalloproteinase activities, and inhibition of integrins. In this study, fibrotic lung injuries were induced in SD rats by a single intratracheal instillation of 5 mg/kg bleomycin (BLM). Then, these rats were administered 7.5, 5, or 2.5 mg/kg PD29 daily for 30 days. BLM induced-syndromes including structure distortion, excessive deposition of ECM, excessive inflammatory infiltration, and pro-inflammatory cytokine release were used to evaluate the protective effect of PD-29. Oxidative stress damage in lung tissues was attenuated by PD29 in a dose-dependent manner. The expression of TGF-β1 and the phosphorylation of Smad-2/-3—its downstream targets—were enhanced by BLM and weakened by PD29. In vitro, PD29 inhibited TGF-β1-induced epithelial-mesenchymal transition (EMT) and transformation in A549 cells and mouse primary fibroblasts into myofibroblasts. In summary, PD29 reversed EMT and transformation of fibroblasts into myofibroblasts in vitro and prevented PF in vivo possibly by suppressing the TGF-β1/Smad pathway.