Peptide PD29 treats bleomycin-induced pulmonary fibrosis by inhibiting the TGF-β/smad signaling pathway
Authors: Ruihe Yu
Huan Bian
Shaochang Jia
Chencheng Li
Bingjing Lin
Guangpan Liu
Chuang Ge
Pengcheng Yu
Hanmei Xu
Zhaohao Zhu
Jialiang Hu
Meng Liu
Guiyue Wu
Qingbo Sun
Journal: Experimental Lung Research (2019)
Discipline: CLINICAL MEDICINE
Keywords: EMT; PD29; Pulmonary fibrosis; TGF-β1/Smad2/3 signaling pathway.
Affiliations: a Jiangsu Provincial Research Center for Synthetic Peptide Drug Discovery and Evaluation, China Pharmaceutical University , Nanjing , Jiangsu , People's Republic of China., b State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University , Nanjing , Jiangsu , People's Republic of China., c Department of Bio-Treatment Jinling Hospital , Nanjing , Jiangsu , People's Republic of China.

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. 

Retracted: No

PubPeer comments:
 The patient groups described in this study appear to look remarkably similar to that of another study by the same research group. In this study, two groups of 45 patients each are described, each with a frostbite-affected finger or toe. Remarkably, the average age of both groups are identical to two groups in a completely different study by the same authors, i.e. X.-H. Zhang, et al., Impact of orally administered tramadol combined with self-selected music on adult outpatients with burns undergoing dressing change: A randomized controlled trial, Burns (2019), https: doi.org 10.1016 j. burns.2019.10.010 (see: https: pubpeer.com publications 372245B45F59B8013E44E2E22E1876) Even though this study has two patient groups with frost-bite-affected fingers or toes, with 31 subjects per group, the average ages are identical to two of the groups in the Burns (2019) paper, which has 45 subjects with severe burn injury per group. Could the authors explain how they reached the exact same average ages in both of these studies? ![file] ,