CoQ10 enhances the efficacy of airway basal stem cell transplantation on bleomycin-induced idiopathic pulmonary fibrosis in mice

Respiratory Research

Weiping Liao¹  Wei Wang¹  Yidi Zhang²  Huanbin Liu²  Jian Xu²  Wenbin Deng²  Yuan Xie²  Jingxin Zhao²  Shuna Liu²  Jinjun Jiang²  Yichu Nie³  Shiyue Li⁴  Yulong Luo⁴ 

[1] Foshan Fourth People’s Hospital, 528000, Foshan, People’s Republic of China;School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, 510275, Guangzhou, People’s Republic of China;School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, 510275, Guangzhou, People’s Republic of China;Clinical Research Institute, The First People’s Hospital of Foshan & Sun Yat-Sen University Foshan Hospital, 528000, Foshan, People’s Republic of China;State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 510120, Guangzhou, People’s Republic of China;

关键词: Idiopathic pulmonary fibrosis (IPF);    Airway basal stem cells (BCs);    Coenzyme Q10 (CoQ10);    Cell transplantation;   

DOI  :  10.1186/s12931-022-01964-4

来源: Springer

【 摘 要 】

BackgroundRecent studies have demonstrated that airway basal stem cells (BCs) transplantation can ameliorate bleomycin-induced idiopathic pulmonary fibrosis (IPF) through lung regeneration promotion. However, BCs under oxidative stress in the alveolar microenvironment are poor in survival, causing unsatisfied efficacy of BCs transplantation. In this study, we investigated whether Coenzyme Q10(CoQ10) counteracts oxidative stress in the alveolar microenvironment, thus improved the efficacy of BCs transplantation for IPF treatment.MethodsThe protective effects of CoQ10 on H2O2-induced BCs apoptosis and cytoplasmic reactive oxygen species (ROS) level were tested by flow cytometry in vitro. The therapeutic effects of BCs combined with CoQ10 were compared to a single BCs transplantation protocol in IPF treatment after 2 weeks and were evaluated by parameters including changes of body weight and survival rate, as well as various levels of pulmonary inflammation, α-SMA expression and hydroxyproline (HYP) in IPF mouse lung tissues.ResultsCoQ10 preincubation with BCs (10 mM, 24 h) significantly reduced the late apoptosis of BCs and the number of oxidative stressful BCs as a result of H2O2 stimulation (1 mM, 6 h) in vitro. IPF mouse model was constructed through bleomycin (5 mg/kg) intratracheal instillation. Bleomycin-induced IPF mice showed weight loss continuously and mortality increased progressively during modeling. Serious pulmonary inflammatory cell infiltration, collagen fiber proliferation, and collagen protein deposition were observed in lung tissues of IPF mice. Though BCs transplantation alone improved indicators above in bleomycin-induced IPF mice to some extent, the combination with CoQ10 improved the transplantation efficacy and obtained better therapeutic effects.ConclusionCoQ10 blocked H2O2-induced apoptosis of BCs and ROS production in vitro, and enhanced the efficacy of BCs transplantation against bleomycin-induced IPF in mice.

【 授权许可】

CC BY