Shan Wang1,2, Xin Wen1,2, Xin-Rui Han1,2, Yong-Jian Wang1,2, Min Shen1,2, Shao-Hua Fan1,2, Juan Zhuang1,3,4, Zi-Feng Zhang1,2, Qun Shan1,2, Meng-Qiu Li1,2, Bin Hu1,2, Chun-Hui Sun1,2, Dong-Mei Wu1,2, Jun Lu1,2, Yuan-Lin Zheng1,2. 1. Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, China. 2. College of Health Sciences, Jiangsu Normal University, Xuzhou, China. 3. School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou, China. 4. Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, School of Life Sciences, Huaiyin Normal University, Huaian, China.
Abstract
OBJECTIVES: Diabetic nephropathy (DN) is a nerve damaging disorder, characterized by glomerular mesangial cell expansion and accumulation of extracellular matrix (ECM) proteins. In this study, we aimed to investigate mesangial cell proliferation and ECM accumulation when promoting or suppressing endogenous miR-382 in glomerular mesangial cells of DN. MATERIALS AND METHODS: Model establishment consisted of DN induction by streptozotocin (STZ) in mice. The underlying regulatory mechanisms of miR-382 were analysed in concert with the treatment of miR-382 mimics, miR-382 inhibitors or siRNA against FoxO1 in cultured glomerular mesangial cells isolated from DN mice. RESULTS: FoxO1 was identified as the downregulated gene in DN based on the microarray data of GSE1009. We found that miR-382 was significantly upregulated in renal tissues of DN mice and its downregulation dephosphorylated FoxO1, reduced glomerular mesangial cell proliferation and ECM accumulation in vitro. The determination of luciferase activity suggested that miR-382 negatively targeted FoxO1. Expectedly, distinct levels of phosphorylated FoxO1 were observed in the renal cortices of DN mice, while the silencing of FoxO1 was found to increase glomerular mesangial cell proliferation and ECM accumulation in vitro. Reduced glomerular mesangial cell proliferation and ECM accumulation elicited by miR-382 inhibitors were reversed by silencing FoxO1. CONCLUSIONS: This study demonstrates miR-382 suppression exerts a potent anti-proliferative effect that may be applied to inhibit glomerular mesangial cell proliferation and ECM accumulation in DN.
OBJECTIVES:Diabetic nephropathy (DN) is a nerve damaging disorder, characterized by glomerular mesangial cell expansion and accumulation of extracellular matrix (ECM) proteins. In this study, we aimed to investigate mesangial cell proliferation and ECM accumulation when promoting or suppressing endogenous miR-382 in glomerular mesangial cells of DN. MATERIALS AND METHODS: Model establishment consisted of DN induction by streptozotocin (STZ) in mice. The underlying regulatory mechanisms of miR-382 were analysed in concert with the treatment of miR-382 mimics, miR-382 inhibitors or siRNA against FoxO1 in cultured glomerular mesangial cells isolated from DN mice. RESULTS:FoxO1 was identified as the downregulated gene in DN based on the microarray data of GSE1009. We found that miR-382 was significantly upregulated in renal tissues of DN mice and its downregulation dephosphorylated FoxO1, reduced glomerular mesangial cell proliferation and ECM accumulation in vitro. The determination of luciferase activity suggested that miR-382 negatively targeted FoxO1. Expectedly, distinct levels of phosphorylated FoxO1 were observed in the renal cortices of DN mice, while the silencing of FoxO1 was found to increase glomerular mesangial cell proliferation and ECM accumulation in vitro. Reduced glomerular mesangial cell proliferation and ECM accumulation elicited by miR-382 inhibitors were reversed by silencing FoxO1. CONCLUSIONS: This study demonstrates miR-382 suppression exerts a potent anti-proliferative effect that may be applied to inhibit glomerular mesangial cell proliferation and ECM accumulation in DN.
Authors: Zhenjiang Ding; Min Qiu; Mohammed A Alharbi; Tiffany Huang; Xiyan Pei; Tatyana N Milovanova; Hongli Jiao; Chanyi Lu; Min Liu; Ling Qin; Dana T Graves Journal: Bone Date: 2021-03-01 Impact factor: 4.626
Authors: Linsey J F Peters; Jürgen Floege; Erik A L Biessen; Joachim Jankowski; Emiel P C van der Vorst Journal: Int J Mol Sci Date: 2020-09-07 Impact factor: 5.923
Authors: Tamil Selvi Loganathan; Siti Aishah Sulaiman; Nor Azian Abdul Murad; Shamsul Azhar Shah; Abdul Halim Abdul Gafor; Rahman Jamal; Noraidatulakma Abdullah Journal: Front Pharmacol Date: 2020-03-03 Impact factor: 5.810