Platycodin D improves pulmonary fibrosis in mice by down-regulating TRPC6 expression and reducing ROS production in lung fibroblasts
10.12122/j.issn.1673-4254.2024.01.08
- VernacularTitle:桔梗素D通过下调成纤维细胞TRPC6表达改善小鼠肺纤维化
- Author:
Zichen LIANG
1
;
Changhui YU
;
Shixiu LIANG
;
Zicong ZHOU
;
Zili ZHOU
;
Xiaojing MENG
;
Fei ZOU
;
Shaoxi CAI
Author Information
1. 南方医科大学南方医院呼吸与危重症医学科,广东 广州 510515
- Keywords:
pulmonary fibrosis;
platycodin D;
transient receptor potential cation channel subfamily C member 6;
reactive oxygen species
- From:
Journal of Southern Medical University
2024;44(1):60-69
- CountryChina
- Language:Chinese
-
Abstract:
Objective To assess the effect of platycodin D(PD)for alleviating pulmonary fibrosis in mice and explore the underlying mechanism.Methods C57BL/6J mouse models of pulmonary fibrosis induced by bleomycin injection into the airway were treated with daily intragastric administration of 10 mg/kg PD for 28 days.The changes of pulmonary fibrosis and the expression and distribution of transient receptor potential cation channel subfamily C member 6(TRPC6)were evaluated with immunohistochemistry,HE staining and Sirius Red staining.Western blotting was used to detect α-SMA expression in the lung tissues of the mice.Primary cultures of mouse lung fibroblasts were pretreated with PD(2.5,5.0,and 10 μmol/L)or larixyl acetate(LA;10 μmol/L)before exposure to 10 ng/mL transforming growth factor-β1(TGF-β1),and the changes in cell survival rate,expressions of collagen I,α-SMA and TRPC6,reactive oxygen species(ROS)production,mitochondrial membrane potential,and cell proliferation capacity were assessed.Network pharmacology analysis was performed to explore the mechanism by which PD alleviated pulmonary fibrosis.Results PD treatment significantly alleviated pulmonary fibrosis and reduced α-SMA expression in BLM-induced mouse models(P<0.05).In TGF-β1-induced primary mouse lung fibroblasts,PD effectively inhibited the cell proliferation,reduced ROS production(P<0.0001),rescued the reduction of mitochondrial membrane potential(P<0.001),and inhibited the expressions of α-SMA and collagenⅠ(P<0.05).Network pharmacology analysis suggested that TRPC6 mediated the effect of PD for alleviating pulmonary fibrosis.Immunohistochemistry showed that PD significantly reduced TRPC6 expression in the lung tissues of BLM-induced mice.In primary mouse lung fibroblasts,PD significantly inhibited TGF-β1-induced TRPC6 expression(P<0.05),and LA treatment obviously lowered the expression levels of TRPC6,α-SMA and collagenⅠ(P<0.05).Conclusion PD alleviated pulmonary fibrosis in mice possibly by down-regulating TRPC6 and reducing ROS production.
