title: SiRNA-HMGA2 weakened AGEs-induced epithelial-to-mesenchymal transition in tubular epithelial cells.
abstract: Diabetic nephropathy as the most common cause of end-stage renal disease accounts for a significant increase in morbidity and mortality in patients. Epithelial to mesenchymal transition (EMT) of tubular cells is associated with diabetic nephropathy. Advanced glycation end products (AGEs) are thought to be involved in the pathogenesis of diabetic nephropathy via multifactorial mechanisms. However, whether AGEs could induce EMT in Tubular epithelial cells is still unknown. In this study, we found that AGEs induced EMT and accompanied by reduced expression of the epithelial markers E-cadherin and enhanced expression of the mesenchymal markers vimentin and alpha-smooth muscle actin. Furthermore, the expression of HMGA2 was upregulated by AGEs. Far more interesting, its knockdown by short interfering RNA (siRNA) effectively reversed AGEs-induced EMT. Meanwhile, we also found that knockdown of HMGA2 inhibited high AGEs-induced generation of reactive oxygen species (ROS) and the activation of p38 MAPK. Collectively, these studies suggest that HMGA2 plays a important role in EMT during Diabetic nephropathy and more study toward HMGA2 should be played in renal pathogenesis.
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Kunming Medical University, Yunnan 650101, China.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Bai
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Kunming Medical University, Yunnan 650101, China.
authors.forename: Jia-Ping
authors.initials: JP
authors.lastname: Wang
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Kunming Medical University, Yunnan 650101, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Kunming Medical University, Yunnan 650101, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Kunming Medical University, Yunnan 650101, China. Electronic address: hongy2014_06@163.com.
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D025743:HMGA2 Protein; D034741:RNA, Small Interfering; D048051:p38 Mitogen-Activated Protein Kinases
keywords: AGEs; EMT; HMGA2