title: Serum response factor induces endothelial-mesenchymal transition in glomerular endothelial cells to aggravate proteinuria in diabetic nephropathy.
abstract: We investigated the expression and function of serum response factor (SRF) in endothelial-mesenchymal transition (EndMT) in glomerular endothelial cells (GEnCs) of diabetic nephropathy (DN). The expression of SRF, endothelial markers (VE-cadherin, CD31), and mesenchymal markers (α-SMA, FSP-1, fibronectin) was examined in GEnCs following high glucose or in renal cortex tissues of DN rats. SRF was upregulated by SRF plasmids and downregulated by CCG-1423 (a small molecule inhibitor of SRF) to investigate how SRF influenced EndMT in GEnCs of DN. Streptozocin (STZ) was used to generate diabetes mellitus DM in rats. In GEnCs after high glucose treatment and in renal cortex tissues of diabetic rats, SRF, α-SMA, FSP-1, and fibronectin increased, while VE-cadherin and CD31 declined. SRF overexpression in GEnCs induced expression of Snail, an important transcription factor mediating EndMT. Blockade of SRF reduced Snail induction, protected GEnCs from EndMT, and ameliorated proteinuria. Together, increased SRF activity provokes EndMT and barrier dysfunction of GEnCs in DN. Targeting SRF by small molecule inhibitor may be an attractive therapeutic strategy for DN.
authors: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
authors: Long
authors: L
authors: Zhao
authors: Department of Nephrology, Shandong Weifang People's Hospital, Weifang, People's Republic of China; and.
authors: Jun
authors: J
authors: Zhao
authors: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
authors: Xueling
authors: X
authors: Wang
authors: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
authors: Zhixin
authors: Z
authors: Chen
authors: Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
authors: Kexin
authors: K
authors: Peng
authors: Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
authors: Xiaohan
authors: X
authors: Lu
authors: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
authors: Linghang
authors: L
authors: Meng
authors: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
authors: Gang
authors: G
authors: Liu
authors: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China; guangj@sdu.edu.cn.
authors: Guangju
authors: G
authors: Guan
authors: Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
authors: Fei
authors: F
authors: Wang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D008297:Male; D011507:Proteinuria / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D015415:Biomarkers; D014157:Transcription Factors; C000620714:serum response factor, rat; D005947:Glucose
keywords: CCG-1423; Snail; diabetic nephropathy; endothelial-mesenchymal transition; glomerular endothelial cells; serum response factor