2. Academic Validation
  3. Rutin alleviates EndMT by restoring autophagy through inhibiting HDAC1 via PI3K/AKT/mTOR pathway in diabetic kidney disease

Rutin alleviates EndMT by restoring autophagy through inhibiting HDAC1 via PI3K/AKT/mTOR pathway in diabetic kidney disease

  • Phytomedicine. 2023 Feb 4;112:154700. doi: 10.1016/j.phymed.2023.154700.
Ruixue Dong 1,  Xi Zhang 2,  Yadi Liu 2,  Tingting Zhao 2,  Zhongyan Sun 2,  Peiyu Liu 2,  Qian Xiang 2,  Jianfeng Xiong 2,  Xinwen Du 2,  Xifei Yang 3,  Dingkun Gui 4,  Youhua Xu 5
Affiliations

Affiliations

  • 1 Faculty of Pharmacy, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao, China.
  • 2 Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao, China.
  • 3 Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020-2024), Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
  • 4 Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Electronic address: dingkungui@sjtu.edu.cn.
  • 5 Faculty of Pharmacy, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao, China; Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao, China; Department of Endocrinology, Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai, China; Zhuhai MUST Science and Technology Research Institute, Macau University of Science and Technology, Hengqin, Zhuhai, China. Electronic address: yhxu@must.edu.mo.
PMID: 36774842 DOI: 10.1016/j.phymed.2023.154700
Abstract

Background: Diabetic kidney disease (DKD) is a primary microvascular complication of diabetes. However, a complete cure for DKD has not yet been found. Although there is evidence that Rutin can delay the onset of DKD, the underlying mechanism remains unclear.

Purpose: To investigate the renoprotective effect of Rutin in the process of DKD and to explore its potential molecular mechanisms.

Methods: Db/db mice and high glucose (HG)-induced human renal glomerular endothelial cells (GEnCs) were used as in vivo and in vitro models, respectively. Western blot (WB), Immunohistochemistry (IHC)and Immunofluorescence (IF) staining were used to identify the expression level of proteins associated with endothelial-to-mesenchymal transition (EndMT) and Autophagy. Tandem Mass Tag (TMT)-based proteomics analysis was utilized to reveal the mechanism of Rutin in DKD. Transfection with small interfering RNA (siRNA) to reveal the role of histone deacetylase 1 (HDAC1) in HG-induced GEnCs.

Results: Following 8 weeks of Rutin administration, db/db mice's kidney function and structure significantly improved. In HG-induced GEnCs, activation of Autophagy attenuates cellular EndMT. Rutin could alleviate EndMT and restore Autophagy in vivo and in vitro models. Proteomics analysis results showed that HDAC1 significantly downregulated in the 200 mg/kg/d Rutin group compared with the db/db group. Transfection with si-HDAC1 in GEnCs partially blocked HG-induced EndMT and restored Autophagy. Furthermore, Rutin inhibits the phosphorylation of the PI3K / Akt/ mTOR pathway. HDAC1 overexpression was suppressed in HG-induced GEnCs after using Rapamycin, a specific mTOR Inhibitor, verifying the correlation between mTOR and HDAC1.

Conclusion: Rutin alleviates EndMT by restoring Autophagy through inhibiting HDAC1 via the PI3K/Akt/mTOR pathway in DKD.

Keywords

Autophagy; Diabetic kidney disease; EndMT; HDAC1; Rutin.

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