Ghrelin Relieves Obesity-Induced Myocardial Injury by Regulating the Epigenetic Suppression of miR-196b Mediated by lncRNA HOTAIR.

Abstract

INTRODUCTION:

Obesity has been believed to be closely linked with many kinds of diseases including atherosclerosis, hypertension, cerebrovascular thrombosis, and diabetes. Ghrelin and Homeobox transcript antisense RNA (HOTAIR) were believed to be involved in the regulation of myocardial injury.

METHODS:

The obesity mice model was established through feeding mice (C57BL/6J, male, eight-week-old) with high-fat diet and palmitate (PA)-induced cardiomyocyte injury. RNA and protein levels were detected with Quantitative real-time PCR and Western blotting. The levels of TG, TCH, LDL, CK-MB, cTnl, and BNP in the serum or cell medium supernatant were measured using ELISA kits. The ROS level was detected with the DCFH-DA method. Binding sites between different targets were identified using detection of dual luciferase reporter assay. Cell apoptosis was analyzed by flow cytometry. RNA-binding protein immunoprecipitation and chromatin immunoprecipitation were used to detect the binding of DNMT3B with HOTAIR or miR-196b promoter.

RESULTS:

The expression of HOTAIR was downregulated, and miR-196b was upregulated in the obese myocardial injury. Ghrelin attenuated PA-induced cardiomyocyte injury by increasing HOTAIR. HOTAIR regulated the expression of miR-196b by recruiting DNMT3B to induce methylation of the miR-196b gene promoter. The binding site between miR-196b and IGF-1 was identified.

DISCUSSION/CONCLUSION:

We demonstrated that ghrelin attenuated PA-induced cardiomyocyte injury by regulating the HOTAIR/miR-196b/IGF-1 signaling pathway. Our findings might provide novel thought for the prevention and treatment of obesity-induced myocardial injury by targeting HOTAIR/miR-196b.

• Authors: Yuan-Yuan Lang, Xin-Yue Xu, Yan-Ling Liu, Chun-Feng Ye, Na Hu, Qing Yao, Wen-Shu Cheng, Zu-Gen Cheng, Yang Liu
• Journal: Obesity facts (Obes Facts) Vol. 15 Issue 4 Pg. 540-549 ( 2022) ISSN: 1662-4033 [Electronic] Switzerland
• PMID: 35294947 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Ghrelin
• HOTAIR long non-coding RNA, mouse
• MIRN196 microRNA, mouse
• MicroRNAs
• RNA, Long Noncoding
• Insulin-Like Growth Factor I

Topics

• Animals
• Epigenesis, Genetic
• Ghrelin
• Insulin-Like Growth Factor I (genetics, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• MicroRNAs (genetics)
• Obesity (complications, genetics)
• RNA, Long Noncoding (genetics)