Bowen Liu1,2, Yunfei Chai1,3, Wei Guo1,4, Kaiyan Lin5, Shiqun Chen1,2, Jin Liu2, Guoli Sun1,2, Guangzhong Chen1,2, Feier Song2, Yibo He2, Yan Liang6, Zhaodong Guo2, Li Lei2,3, Lihao He1,2, Liwei Liu2, Ning Tan1,2,3, Yong Liu1,2,7, Shilong Zhong1,2,7, Jiyan Chen1,2,7. 1. Guangdong Provincial People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510000, China. 2. Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China. 3. Department of Anesthesiology, Cardiovascular Institute of Guangdong Province, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China. 4. Guangdong Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China. 5. Department of Cardiology, Fujian Provincial Hospital, Fujian Medical University, Fujian Cardiovascular Institute, Fuzhou 350001, China. 6. Department of Cardiology, Maoming People's Hospital, Maoming 525000, China. 7. The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.
Abstract
BACKGROUND: Contrast media (CM) is widely used in cardiac catheterization; however, it may cause contrast-induced acute kidney injury (CI-AKI) which severely increases mortality. MicroRNA (miRNA) has been found to participate in the process of acute kidney injury (AKI), and this discovery has great potential for diagnosis and treatment. However, the role of miRNA in CI-AKI is still unclear. This study aimed to investigate the regulatory effect miRNAs exert in CI-AKI. METHODS: We established a novel, representative, isotonic CI-AKI model by using CM iodixanol, a CM which is commonly used in clinic. Next-generation sequencing and reverse transcription polymerase chain reaction (RT-qPCR) were performed to determine the expression of miRNA-188 in CI-AKI. Western blot analysis of the apoptosis regulator protein and TUNEL assay were ordered to evaluate apoptosis. Bioinformatics and double luciferin reporter gene assay were performed to predict and to confirm the interaction between microRNA-188 and SRSF7. RESULTS: The novel isotonic CI-AKI rat model we established exhibited typical characteristics of CI-AKI in serum creatinine, cystatin C, HE staining, and under electron microscope observation. Sequencing and RT-qPCR demonstrated that miRNA-188 was significantly up-regulated both in CI-AKI rat and HK-2 cell models while overexpression of miRNA-188 significantly aggravated apoptosis in CI-AKI cell models. SRSF7 was identified as a direct target gene of miRNA-188, and dual luciferase reporter assay determined the direct interaction between SRSF7 and miRNA-188. In addition, SRSF7 silencing reduced the cell viability rate of the CI-AKI cell model. CONCLUSIONS: The present study's findings indicate that miRNA-188 aggravated contrast-induced apoptosis by regulating SRSF7, which may serve as a potential drug target for CI-AKI intervention.
BACKGROUND: Contrast media (CM) is widely used in cardiac catheterization; however, it may cause contrast-induced acute kidney injury (CI-AKI) which severely increases mortality. MicroRNA (miRNA) has been found to participate in the process of acute kidney injury (AKI), and this discovery has great potential for diagnosis and treatment. However, the role of miRNA in CI-AKI is still unclear. This study aimed to investigate the regulatory effect miRNAs exert in CI-AKI. METHODS: We established a novel, representative, isotonic CI-AKI model by using CM iodixanol, a CM which is commonly used in clinic. Next-generation sequencing and reverse transcription polymerase chain reaction (RT-qPCR) were performed to determine the expression of miRNA-188 in CI-AKI. Western blot analysis of the apoptosis regulator protein and TUNEL assay were ordered to evaluate apoptosis. Bioinformatics and double luciferin reporter gene assay were performed to predict and to confirm the interaction between microRNA-188 and SRSF7. RESULTS: The novel isotonic CI-AKI rat model we established exhibited typical characteristics of CI-AKI in serum creatinine, cystatin C, HE staining, and under electron microscope observation. Sequencing and RT-qPCR demonstrated that miRNA-188 was significantly up-regulated both in CI-AKI rat and HK-2 cell models while overexpression of miRNA-188 significantly aggravated apoptosis in CI-AKI cell models. SRSF7 was identified as a direct target gene of miRNA-188, and dual luciferase reporter assay determined the direct interaction between SRSF7 and miRNA-188. In addition, SRSF7 silencing reduced the cell viability rate of the CI-AKI cell model. CONCLUSIONS: The present study's findings indicate that miRNA-188 aggravated contrast-induced apoptosis by regulating SRSF7, which may serve as a potential drug target for CI-AKI intervention.
Authors: Bernhard Gentner; Giulia Schira; Alice Giustacchini; Mario Amendola; Brian D Brown; Maurilio Ponzoni; Luigi Naldini Journal: Nat Methods Date: 2008-11-30 Impact factor: 28.547
Authors: Charanjit S Rihal; Stephen C Textor; Diane E Grill; Peter B Berger; Henry H Ting; Patricia J Best; Mandeep Singh; Malcolm R Bell; Gregory W Barsness; Verghese Mathew; Kirk N Garratt; David R Holmes Journal: Circulation Date: 2002-05-14 Impact factor: 29.690
Authors: Vincenzo Cantaluppi; Stefano Gatti; Davide Medica; Federico Figliolini; Stefania Bruno; Maria C Deregibus; Andrea Sordi; Luigi Biancone; Ciro Tetta; Giovanni Camussi Journal: Kidney Int Date: 2012-04-11 Impact factor: 10.612
Authors: Mangiring P L Toruan; Raymond Pranata; Budi Yuli Setianto; Sofia Mubarika Haryana Journal: Biomed Res Int Date: 2020-05-21 Impact factor: 3.411