title: Effects and mechanism of miR-23b on glucose-mediated epithelial-to-mesenchymal transition in diabetic nephropathy.
abstract: MicroRNAs (miRNAs) play important roles in epithelial-to-mesenchymal transition (EMT). Moreover, hyperglycaemia induces damage to renal tubular epithelial cells, which may lead to EMT in diabetic nephropathy. However, the effects of miRNAs on EMT in diabetic nephropathy are poorly understood. In the present study, we found that the level of microRNA-23b (miR-23b) was significantly decreased in high glucose (HG)-induced human kidney proximal tubular epithelial cells (HK2) and in kidney tissues of db/db mice. Overexpression of miR-23b attenuated HG-induced EMT, whereas knockdown of miR-23b induced normal glucose (NG)-mediated EMT in HK2 cells. Mechanistically, miR-23b suppressed EMT in diabetic nephropathy by targeting high mobility group A2 (HMGA2), thereby repressing PI3K-AKT signalling pathway activation. Additionally, HMGA2 knockdown or inhibition of the PI3K-AKT signalling pathway with LY294002 mimicked the effects of miR-23b overexpression on HG-mediated EMT, whereas HMGA2 overexpression or activation of the PI3K-AKT signalling pathway with BpV prevented the effects of miR-23b on HG-mediated EMT. We also confirmed that overexpression of miR-23b alleviated EMT, decreased the expression levels of EMT-related genes, ameliorated renal morphology, glycogen accumulation, fibrotic responses and improved renal functions in db/db mice. Taken together, we showed for the first time that miR-23b acts as a suppressor of EMT in diabetic nephropathy through repressing PI3K-AKT signalling pathway activation by targeting HMGA2, which maybe a potential therapeutic target for diabetes-induced renal dysfunction.
authors.affiliation: Department of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, PR China; Heilongjiang Province Key Laboratory for Anti-Fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, PR China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Laboratory of Pathogenic Microbiology and Immunology, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, PR China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, PR China.
authors.forename: Shengfeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: Heilongjiang Province Key Laboratory for Anti-Fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, PR China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Li
authors.affiliation: Heilongjiang Province Key Laboratory for Anti-Fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, PR China.
authors.forename: Xiaohuan
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Heilongjiang Province Key Laboratory for Anti-Fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, PR China.
authors.forename: Biao
authors.initials: B
authors.lastname: Feng
authors.affiliation: Heilongjiang Province Key Laboratory for Anti-Fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Bai
authors.affiliation: Heilongjiang Province Key Laboratory for Anti-Fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, PR China. Electronic address: zhaobinghai01@163.com.
authors.forename: Binghai
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Heilongjiang Province Key Laboratory for Anti-Fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, PR China. Electronic address: yanhui_chu@sina.com.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, PR China. Electronic address: tlihj@jnu.edu.cn.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D006003:Glycogen / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009843:Oligoribonucleotides / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002867:Chromones; D005947:Glucose; D006003:Glycogen; D025743:HMGA2 Protein; D035683:MicroRNAs; D009025:Morpholines; D009843:Oligoribonucleotides; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C552430:MIRN23a microRNA, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: Diabetic nephropathy; Epithelial-to-mesenchymal transition (EMT); HMGA2; Mir-23b; Renal tubular epithelial cell