Chunping Zhu1, Haijun Zhang2, Dongmei Wei3, Zhe Sun4. 1. Department of Cardiac Function, The First Hospital of Qiqihar & Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, 161005, Heilongjiang, People's Republic of China. 2. The Second Department of Endocrinology, The First Hospital of Qiqihar & Affiliated Qiqihar Hospital, Southern Medical University, No. 30 Park Road, Longsha, Qiqihar, 161005, Heilongjiang, People's Republic of China. haijunzhangqiqihar@163.com. 3. Department of Traditional Chinese Medicine Geriatrics, The First Hospital of Qiqihar & Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, 161005, Heilongjiang, People's Republic of China. 4. The Second Department of Endocrinology, The First Hospital of Qiqihar & Affiliated Qiqihar Hospital, Southern Medical University, No. 30 Park Road, Longsha, Qiqihar, 161005, Heilongjiang, People's Republic of China.
Abstract
BACKGROUND: LncRNA GAS5 is associated with high glucose-induced cardiomyocyte injury, but its role in diabetic cardiomyopathy (DCM) remains unclear. METHODS: Mice were administered with streptozotocin to construct the diabetic model (DM). Primary mouse cardiomyocytes were isolated and treated with 30 mmol/L high glucose to mimic the diabetic condition in vitro. GAS5 expression was detected by quantitative reverse transcription polymerase chain reaction. The relationship between GAS5 and miR-26a/b-5p was determined by bioinformatic prediction, luciferase reporter assay and RNA immunoprecipitation assay. The cardiac function of diabetic mice was evaluated by two-dimensional echocardiography. RESULTS: GAS5 was significantly upregulated in diabetic cardiomyopathy both in vitro and in vivo. GAS5 knockdown and miR-26a/b-5p overexpression not only effectively attenuated myocardial fibrosis of diabetic mice in vivo but also inhibited high glucose-induced cardiomyocyte injury in vitro. miR-26a/b-5p was identified as a target of GAS5. GAS5 knockdown efficiently attenuated myocardial fibrosis and high glucose-induced cardiomyocyte injury through negatively regulating miR-26a/b-p. CONCLUSION: Our study showed that GAS5 promotes DCM progression by regulating miR-26a/b-5p, suggesting that GAS5 might be a potential therapeutic target for DCM.
BACKGROUND: LncRNA GAS5 is associated with high glucose-induced cardiomyocyte injury, but its role in diabetic cardiomyopathy (DCM) remains unclear. METHODS:Mice were administered with streptozotocin to construct the diabetic model (DM). Primary mouse cardiomyocytes were isolated and treated with 30 mmol/L high glucose to mimic the diabetic condition in vitro. GAS5 expression was detected by quantitative reverse transcription polymerase chain reaction. The relationship between GAS5 and miR-26a/b-5p was determined by bioinformatic prediction, luciferase reporter assay and RNA immunoprecipitation assay. The cardiac function of diabeticmice was evaluated by two-dimensional echocardiography. RESULTS:GAS5 was significantly upregulated in diabetic cardiomyopathy both in vitro and in vivo. GAS5 knockdown and miR-26a/b-5p overexpression not only effectively attenuated myocardial fibrosis of diabeticmice in vivo but also inhibited high glucose-induced cardiomyocyte injury in vitro. miR-26a/b-5p was identified as a target of GAS5. GAS5 knockdown efficiently attenuated myocardial fibrosis and high glucose-induced cardiomyocyte injury through negatively regulating miR-26a/b-p. CONCLUSION: Our study showed that GAS5 promotes DCM progression by regulating miR-26a/b-5p, suggesting that GAS5 might be a potential therapeutic target for DCM.
Authors: Yi Tan; Zhiguo Zhang; Chao Zheng; Kupper A Wintergerst; Bradley B Keller; Lu Cai Journal: Nat Rev Cardiol Date: 2020-02-20 Impact factor: 32.419
Authors: Tyler N Kambis; Hadassha M N Tofilau; Flobater I Gawargi; Surabhi Chandra; Paras K Mishra Journal: Curr Diab Rep Date: 2021-12-13 Impact factor: 4.810