Hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by Hmgcs2, promoting high glucose‐induced cardiomyocyte injury
Abstract Background Diabetic cardiomyopathy (DCM) represents a major cause of heart failure and a large medical burden worldwide. This study screened the potentially regulatory targets of DCM and analyzed their roles in high glucose (HG)‐induced cardiomyocyte injury. Methods Through GEO database, we...
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Wiley
2024-03-01
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| Series: | Immunity, Inflammation and Disease |
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| Online Access: | https://doi.org/10.1002/iid3.1191 |
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| author | Ying Wang Li‐Feng Ping Fu‐Yan Bai Xin‐Huan Zhang Guang‐Hong Li |
| author_facet | Ying Wang Li‐Feng Ping Fu‐Yan Bai Xin‐Huan Zhang Guang‐Hong Li |
| author_sort | Ying Wang |
| collection | DOAJ |
| description | Abstract Background Diabetic cardiomyopathy (DCM) represents a major cause of heart failure and a large medical burden worldwide. This study screened the potentially regulatory targets of DCM and analyzed their roles in high glucose (HG)‐induced cardiomyocyte injury. Methods Through GEO database, we obtained rat DCM expression chips and screened differentially expressed genes. Rat cardiomyocytes (H9C2) were induced with HG. 3‐hydroxy‐3‐methylglutarylcoenzyme A synthase 2 (Hmgcs2) and microRNA (miR)‐363‐5p expression patterns in cells were measured by real‐time quantitative polymerase chain reaction or Western blot assay, with the dual‐luciferase assay to analyze their binding relationship. Then, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide assay, lactate dehydrogenase assay, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, enzyme‐linked immunosorbent assay, and various assay kits were applied to evaluate cell viability, cytotoxicity, apoptosis, inflammation responses, and oxidative burden. Results Hmgcs2 was the vital hub gene in DCM. Hmgcs2 was upregulated in HG‐induced cardiomyocytes. Hmgcs2 downregulation increased cell viability, decreased TUNEL‐positive cell number, reduced HG‐induced inflammation and oxidative stress. miR‐363‐5p is the upstream miRNA of Hmgcs2. miR‐363‐5p overexpression attenuated HG‐induced cell injury. Conclusions Hmgcs2 had the most critical regulatory role in DCM. We for the first time reported that miR‐363‐5p inhibited Hmgcs2 expression, thereby alleviating HG‐induced cardiomyocyte injury. |
| first_indexed | 2024-04-24T18:40:38Z |
| format | Article |
| id | doaj.art-1c90f607e7ee4612a3278a80e648c435 |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-04-24T18:40:38Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-1c90f607e7ee4612a3278a80e648c4352024-03-27T12:16:38ZengWileyImmunity, Inflammation and Disease2050-45272024-03-01123n/an/a10.1002/iid3.1191Hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by Hmgcs2, promoting high glucose‐induced cardiomyocyte injuryYing Wang0Li‐Feng Ping1Fu‐Yan Bai2Xin‐Huan Zhang3Guang‐Hong Li4Department of Endocrinology The Second Affiliated Hospital of Shandong First Medical University Tai'an ChinaDepartment of General Medicine The Second Affiliated Hospital of Shandong First Medical University Tai'an ChinaDepartment of Endocrinology The Second Affiliated Hospital of Shandong First Medical University Tai'an ChinaDepartment of Endocrinology The Second Affiliated Hospital of Shandong First Medical University Tai'an ChinaDepartment of Endocrinology The Second Affiliated Hospital of Shandong First Medical University Tai'an ChinaAbstract Background Diabetic cardiomyopathy (DCM) represents a major cause of heart failure and a large medical burden worldwide. This study screened the potentially regulatory targets of DCM and analyzed their roles in high glucose (HG)‐induced cardiomyocyte injury. Methods Through GEO database, we obtained rat DCM expression chips and screened differentially expressed genes. Rat cardiomyocytes (H9C2) were induced with HG. 3‐hydroxy‐3‐methylglutarylcoenzyme A synthase 2 (Hmgcs2) and microRNA (miR)‐363‐5p expression patterns in cells were measured by real‐time quantitative polymerase chain reaction or Western blot assay, with the dual‐luciferase assay to analyze their binding relationship. Then, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide assay, lactate dehydrogenase assay, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, enzyme‐linked immunosorbent assay, and various assay kits were applied to evaluate cell viability, cytotoxicity, apoptosis, inflammation responses, and oxidative burden. Results Hmgcs2 was the vital hub gene in DCM. Hmgcs2 was upregulated in HG‐induced cardiomyocytes. Hmgcs2 downregulation increased cell viability, decreased TUNEL‐positive cell number, reduced HG‐induced inflammation and oxidative stress. miR‐363‐5p is the upstream miRNA of Hmgcs2. miR‐363‐5p overexpression attenuated HG‐induced cell injury. Conclusions Hmgcs2 had the most critical regulatory role in DCM. We for the first time reported that miR‐363‐5p inhibited Hmgcs2 expression, thereby alleviating HG‐induced cardiomyocyte injury.https://doi.org/10.1002/iid3.1191diabetic cardiomyopathyGEO database chiphigh glucosehmgcs2miR‐363‐5p |
| spellingShingle | Ying Wang Li‐Feng Ping Fu‐Yan Bai Xin‐Huan Zhang Guang‐Hong Li Hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by Hmgcs2, promoting high glucose‐induced cardiomyocyte injury Immunity, Inflammation and Disease diabetic cardiomyopathy GEO database chip high glucose hmgcs2 miR‐363‐5p |
| title | Hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by Hmgcs2, promoting high glucose‐induced cardiomyocyte injury |
| title_full | Hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by Hmgcs2, promoting high glucose‐induced cardiomyocyte injury |
| title_fullStr | Hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by Hmgcs2, promoting high glucose‐induced cardiomyocyte injury |
| title_full_unstemmed | Hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by Hmgcs2, promoting high glucose‐induced cardiomyocyte injury |
| title_short | Hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by Hmgcs2, promoting high glucose‐induced cardiomyocyte injury |
| title_sort | hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by hmgcs2 promoting high glucose induced cardiomyocyte injury |
| topic | diabetic cardiomyopathy GEO database chip high glucose hmgcs2 miR‐363‐5p |
| url | https://doi.org/10.1002/iid3.1191 |
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