Diabetes & Metabolism Journal

Response

Diabetes Promotes Myocardial Fibrosis via AMPK/EZH2/PPAR-γ Signaling Pathway (Diabetes Metab J 2024;48:716-29): Shan-Shan Li, Lu Pan, Shipeng Dang, Ru-Xing Wang; Diabetes Metab J. 2024;48(6):1181-1182. Published online November 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0675

1,874 View
38 Download

PDF PubReader ePub

Original Article

Basic Research
Diabetes Promotes Myocardial Fibrosis via AMPK/EZH2/PPAR-γ Signaling Pathway: Shan-Shan Li, Lu Pan, Zhen-Ye Zhang, Meng-Dan Zhou, Xu-Fei Chen, Ling-Ling Qian, Min Dai, Juan Lu, Zhi-Ming Yu, Shipeng Dang, Ru-Xing Wang; Diabetes Metab J. 2024;48(4):716-729. Published online February 27, 2024; DOI: https://doi.org/10.4093/dmj.2023.0031

8,511 View
315 Download
15 Web of Science
15 Crossref

Background
Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified.
Methods
In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed.
Results
In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation.
Conclusion
Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

Citations

Citations to this article as recorded by

A Computational Approach to Identify Novel Protein Targets Uncovers New Potential Mechanisms of Action of Mirtazapine S(+) and R(−) Enantiomers in Rett Syndrome
Ottavia Maria Roggero, Nicolò Gualandi, Viviana Ciraci, Vittoria Berutto, Emanuele Carosati, Enrico Tongiorgi
Journal of Neurochemistry.2025;[Epub] CrossRef
ER-α36 prevents high glucose-induced cellular senescence and apoptosis in renal tubular cell
Dehai Yu, Ling Luo, Yu Liang, Huili Zhou, Yinghui Xiao, Xingna An, Yingzhao Wang, Zhonggao Xu, Weixia Sun, Wanning Wang
Frontiers in Endocrinology.2025;[Epub] CrossRef
EZH2 in non-cancerous diseases: expanding horizons
Renjing Jin, Jianlin Zhang, Yuqing Wang, Ziyu Chen, Xuan He, Xintong Zhang, Zhen Tan, Celina G Kleer, Ye Li, Deli Wang, Lixiang Xue
Protein & Cell.2025;[Epub] CrossRef
Nuclear receptors in metabolism and diseases: Mechanistic and therapeutic insights
Chen-Ying Zhu, Pei-Han Yu, Qi Sun, De-Fei Hong, Chang Yang, Hua Naranmandura
Pharmacological Research.2025; 218: 107862. CrossRef
Epigenetics Plays a Role in the Pathogenesis and Treatment of Diabetes
Kajetan Kiełbowski, Estera Bakinowska, Andrzej Pawlik
Genes.2025; 16(7): 769. CrossRef
UM-164 alleviates high starch diet-induced hepatic abnormal lipid accumulation via inhibiting pentose phosphate pathway and mTOR-SREBPs signaling in channel catfish (Ictalurus punctatus)
Qisheng Lu, Xiaochen Ma, Guoli Han, Jinglu Jia, Jingyue Cao, Haokun Liu, Junyan Jin, Zhimin Zhang, Yunxia Yang, Xiaoming Zhu, Shouqi Xie, Dong Han
Aquaculture Reports.2025; 44: 103031. CrossRef
Β-Hydroxybutyrate inhibits centriole duplication and mitochondrial dysfunction through β-hydroxybutyrylation of ANXA11 in diabetic cardiomyopathy rats
Jingyu Liu, Bin Wu, Xin Nian, Shiying Huang, Yaxian Song, Yaxin Guan, Fang Sun, Xiao Meng, Shengting Huang
Cellular Signalling.2025; 136: 112086. CrossRef
The role of AMPK signaling pathway in the pathogenesis of type 2 diabetes mellitus with its complications and related metabolic disorders
Kibur Hunie Tesfa, Chernet Desalegn Gebeyehu, Asrat Tadele Ewunetie, Endalkachew Gugsa, Amare Nigatu Zewdie, Gashaw Dessie, Hiwot Tezera Endale
Metabolism Open.2025; 28: 100397. CrossRef
Metabolic-epigenetic interactions in heart failure: Current understanding and future directions
Benjamin Flowers, Bea Duric
Biochemical and Biophysical Research Communications.2025; 783: 152608. CrossRef
Cardiometabolic Therapies Shape Non-Coding RNA Landscapes in Cardiovascular Fibrosis
Erica Floris, Francesco Nutile, Claudia Cozzolino, Virginia Pontecorvi, Antonella Bordin, Elena De Falco, Vittorio Picchio, Isotta Chimenti, Francesca Pagano
Metabolites.2025; 15(10): 664. CrossRef
Emerging in Diabetic Cardiomyopathy: Molecular Pathways and Targets for Therapeutic Intervention
Mansi Vinodkumar Trivedi, Hemant R. Jadhav, Anil Bhanudas Gaikwad
Drug Development Research.2025;[Epub] CrossRef
An update on chronic complications of diabetes mellitus: from molecular mechanisms to therapeutic strategies with a focus on metabolic memory
Tongyue Yang, Feng Qi, Feng Guo, Mingwei Shao, Yi Song, Gaofei Ren, Zhao Linlin, Guijun Qin, Yanyan Zhao
Molecular Medicine.2024;[Epub] CrossRef
Farrerol Alleviates Diabetic Cardiomyopathy by Regulating AMPK-Mediated Cardiac Lipid Metabolic Pathways in Type 2 Diabetic Rats
Jia Tu, Qiaoling Liu, Huirong Sun, Luzhen Gan
Cell Biochemistry and Biophysics.2024; 82(3): 2427. CrossRef
Diabetes Promotes Myocardial Fibrosis via AMPK/EZH2/PPAR-γ Signaling Pathway (Diabetes Metab J 2024;48:716-29)
Shan-Shan Li, Lu Pan, Shipeng Dang, Ru-Xing Wang
Diabetes & Metabolism Journal.2024; 48(6): 1181. CrossRef
Targeting Cardiac Fibrosis in Diabetic Heart Failure: The Role of the EZH2, AMPK, and PPAR-γ Pathways (Diabetes Metab J 2024;48:716-29)
Jooyeop Lee, Joon Ho Moon
Diabetes & Metabolism Journal.2024; 48(6): 1176. CrossRef

First
Prev
Page of 1
Next
Last

Search