Peimine ameliorates pulmonary fibrosis via the inhibition of M2-type macrophage polarization through the suppression of P38/Akt/STAT6 signals.

Abstract

Peimine, a bioactive substance isolated from Chinese medicine Fritillaria, can potentially suppress pulmonary fibrosis (PF); however, its therapeutic mechanism remains unclear. Recent evidence suggests the participation of M2-type macrophages in the pathogenesis of PF. The present study aimed to investigate the effect of peimine on a bleomycin (BLM)-induced PF rat model and the underlying mechanism of this effect. After BLM administration, peimine was administered to rats from day 29 to day 42, with pirfenidone (PFD) as a positive control. H&E and Masson's trichrome stain were used to analyze histological changes. Q-PCR and western blotting were used to measure mRNA levels and protein levels, respectively. High-throughput RNA sequencing (RNA-seq) technology detected the differentially expressed genes (DEGs) regulated by peimine. Our results revealed that peimine treatment significantly ameliorated BLM-induced PF by suppressing histological changes and collagen deposition. In addition, peimine decreased the number of M2 macrophages and the expression of profibrotic factors. RNA-seq results showed that DEGs regulated by peimine in IL-4-induced macrophages were mainly associated with immune system processes, the PI3K/Akt pathway, and the MAPKs pathway. Then, immunofluorescence assay and western blot results demonstrated that peimine treatment suppressed the expression of p-p38 MAPK and p-Akt (s473) and also inhibited the nuclear translocation of p-STAT6. In conclusion, the present study demonstrated that peimine has a protective effect on PF through the suppression of M2 polarization of macrophages by inhibiting the STAT6, p38 MAPK, and Akt signals.

• Authors: Ze-Hui Cai, Yan-Ge Tian, Jun-Zi Li, Peng Zhao, Jian-Sheng Li, Xue Mei, Yun-Ping Bai
• Journal: Bioscience reports (Biosci Rep) Vol. 42 Issue 10 (10 28 2022) ISSN: 1573-4935 [Electronic] England
• PMID: 36111628 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Author(s).

Chemical References

• Cevanes
• RNA, Messenger
• STAT6 Transcription Factor
• Bleomycin
• Interleukin-4
• verticine
• Collagen
• Proto-Oncogene Proteins c-akt
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Bleomycin
• Cevanes
• Collagen (metabolism)
• Interleukin-4 (metabolism)
• Macrophages (metabolism)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Pulmonary Fibrosis (chemically induced, drug therapy, genetics)
• RNA, Messenger (metabolism)
• Rats
• STAT6 Transcription Factor (metabolism)
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)