108139
论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
- 3.4 Breast Cancer (Dove Med Press)
- 3.2 Clin Epidemiol
- 2.6 Cancer Manag Res
- 2.9 Infect Drug Resist
- 3.7 Clin Interv Aging
- 5.1 Drug Des Dev Ther
- 3.1 Int J Chronic Obstr
- 6.6 Int J Nanomed
- 2.6 Int J Women's Health
- 2.9 Neuropsych Dis Treat
- 2.8 OncoTargets Ther
- 2.0 Patient Prefer Adher
- 2.2 Ther Clin Risk Manag
- 2.5 J Pain Res
- 3.0 Diabet Metab Synd Ob
- 3.2 Psychol Res Behav Ma
- 3.4 Nat Sci Sleep
- 1.8 Pharmgenomics Pers Med
- 2.0 Risk Manag Healthc Policy
- 4.1 J Inflamm Res
- 2.0 Int J Gen Med
- 3.4 J Hepatocell Carcinoma
- 3.0 J Asthma Allergy
- 2.2 Clin Cosmet Investig Dermatol
- 2.4 J Multidiscip Healthc
已发表论文
醛糖还原酶介导的线粒体自噬促进肝细胞上皮间质转化
Authors Yan J, Zhao W, Wang H, Zhou L, Li X, Wang G
Received 11 June 2025
Accepted for publication 12 September 2025
Published 1 October 2025 Volume 2025:17 Pages 141—159
DOI https://doi.org/10.2147/HMER.S546357
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Gerry Lake-Bakaar
Jingjing Yan,1 Wenke Zhao,1 Haoyu Wang,1 Lutan Zhou,1 Xianwei Li,1 Guannan Wang2
1Department of Pharmacy, Wannan Medical College, Wuhu, Anhui, 241002, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241001, People’s Republic of China
Correspondence: Guannan Wang, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, No.2 Zheshan West Road, Wuhu, Anhui, 241001, People’s Republic of China, Email guannanwang81@126.com Xianwei Li, Department of Pharmacy, Wannan Medical College, No. 22 West Wenchang Road, Wuhu, Anhui, 241002, People’s Republic of China, Email lxw0075@wnmc.edu.cn
Background: Recent studies suggest that impaired mitophagy leading to epithelial-mesenchymal transition (EMT) in hepatocytes plays a major role in the progression of hepatic fibrosis (HF). The authors’ previous study demonstrated that aldose reductase (AR) promotes radiation-induced EMT in alveolar epithelial cells. This study aims to examine whether AR influences EMT in hepatocytes by regulating defective mitophagy.
Methods: Some histological techniques, including HE staining, Masson’s trichrome staining, immunohistochemistry, and transmission electron microscopy, were employed to validate the model and examine mitochondrial injury. Subsequently, EMT was induced in hepatocytes through TGF-β 1 treatment. Then experiments such as siRNA-mediated gene silencing, AR inhibition, and AR overexpression were performed. Finally, the activation status of AKT and mTOR, as well as the expression levels of proteins associated with mitophagy and EMT, were evaluated using RT-qPCR, immunofluorescence staining, and Western blotting.
Results: AR knockout significantly reduced AKT and mTOR phosphorylation In vivo but increased the expression of Pink1 and Parkin in CCl4-exposed liver tissues. This was associated with an increased LC3 II/I expression ratio, decreased p62 expression, reduced mitochondrial damage, enhanced E-cadherin expression, and diminished Snail, α-SMA, and vimentin expression, which collectively alleviated HF. In vitro experiments revealed that AR knockdown significantly attenuated the activation of the TGF-β 1-induced AKT/mTOR pathway, restored mitochondrial autophagy function, decreased ROS levels, increased mitochondrial membrane potential (MMP) and ATP production, and reversed EMT in hepatocytes via siRNA or pharmacological inhibition. Conversely, AR overexpression exacerbated the activation of the TGF-β 1-induced AKT/mTOR pathway, impaired mitophagy efficiency, increased ROS levels, decreased MMP and ATP levels, and facilitated EMT process.
Conclusion: The study findings demonstrated that AR facilitates EMT in hepatocytes and plays a major role in enhancing HF. This process may be linked to AR-induced activation of the AKT/mTOR. Consequently, this activation suppresses the expression of Pink1 and Parkin, ultimately reducing the risk of mitophagy in hepatocytes.
Keywords: aldose reductase, hepatic fibrosis, epithelial-mesenchymal transition, mitophagy
1Department of Pharmacy, Wannan Medical College, Wuhu, Anhui, 241002, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241001, People’s Republic of China
Correspondence: Guannan Wang, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, No.2 Zheshan West Road, Wuhu, Anhui, 241001, People’s Republic of China, Email guannanwang81@126.com Xianwei Li, Department of Pharmacy, Wannan Medical College, No. 22 West Wenchang Road, Wuhu, Anhui, 241002, People’s Republic of China, Email lxw0075@wnmc.edu.cn
Background: Recent studies suggest that impaired mitophagy leading to epithelial-mesenchymal transition (EMT) in hepatocytes plays a major role in the progression of hepatic fibrosis (HF). The authors’ previous study demonstrated that aldose reductase (AR) promotes radiation-induced EMT in alveolar epithelial cells. This study aims to examine whether AR influences EMT in hepatocytes by regulating defective mitophagy.
Methods: Some histological techniques, including HE staining, Masson’s trichrome staining, immunohistochemistry, and transmission electron microscopy, were employed to validate the model and examine mitochondrial injury. Subsequently, EMT was induced in hepatocytes through TGF-β 1 treatment. Then experiments such as siRNA-mediated gene silencing, AR inhibition, and AR overexpression were performed. Finally, the activation status of AKT and mTOR, as well as the expression levels of proteins associated with mitophagy and EMT, were evaluated using RT-qPCR, immunofluorescence staining, and Western blotting.
Results: AR knockout significantly reduced AKT and mTOR phosphorylation In vivo but increased the expression of Pink1 and Parkin in CCl4-exposed liver tissues. This was associated with an increased LC3 II/I expression ratio, decreased p62 expression, reduced mitochondrial damage, enhanced E-cadherin expression, and diminished Snail, α-SMA, and vimentin expression, which collectively alleviated HF. In vitro experiments revealed that AR knockdown significantly attenuated the activation of the TGF-β 1-induced AKT/mTOR pathway, restored mitochondrial autophagy function, decreased ROS levels, increased mitochondrial membrane potential (MMP) and ATP production, and reversed EMT in hepatocytes via siRNA or pharmacological inhibition. Conversely, AR overexpression exacerbated the activation of the TGF-β 1-induced AKT/mTOR pathway, impaired mitophagy efficiency, increased ROS levels, decreased MMP and ATP levels, and facilitated EMT process.
Conclusion: The study findings demonstrated that AR facilitates EMT in hepatocytes and plays a major role in enhancing HF. This process may be linked to AR-induced activation of the AKT/mTOR. Consequently, this activation suppresses the expression of Pink1 and Parkin, ultimately reducing the risk of mitophagy in hepatocytes.
Keywords: aldose reductase, hepatic fibrosis, epithelial-mesenchymal transition, mitophagy