title: Critical role of serum response factor in podocyte epithelial-mesenchymal transition of diabetic nephropathy.
abstract: OBJECTIVE
  To investigate the expression and function of serum response factor in podocyte epithelial-mesenchymal transition of diabetic nephropathy.
  
  
  METHODS
  The expression of serum response factor, epithelial markers and mesenchymal markers was examined in podocytes or renal cortex tissues following high glucose. Serum response factor was upregulated by its plasmids and downregulated by CCG-1423 to investigate how it influenced podocyte epithelial-mesenchymal transition in diabetic nephropathy. Streptozotocin was used to generate diabetes mellitus in rats.
  
  
  RESULTS
  In podocytes after high glucose treatment, serum response factor and mesenchymal markers increased, while epithelial markers declined. Similar changes were observed in vivo. Serum response factor overexpression in podocytes induced expression of Snail, an important transcription factor mediating epithelial-mesenchymal transition. Blockade of serum response factor reduced Snail induction, protected podocytes from epithelial-mesenchymal transition and ameliorated proteinuria.
  
  
  CONCLUSIONS
  Together, increased serum response factor activity provokes podocytes' epithelial-mesenchymal transition and dysfunction in diabetic nephropathy. Targeting serum response factor by small-molecule inhibitor may be an attractive therapeutic strategy for diabetic nephropathy.
authors.affiliation: Nephrology Research Institute, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Nephrology Research Institute, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Wang
authors.affiliation: Nephrology Research Institute, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
authors.forename: Lina
authors.initials: L
authors.lastname: Sun
authors.affiliation: Nephrology Research Institute, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
authors.forename: Huibin
authors.initials: H
authors.lastname: Nie
authors.affiliation: Nephrology Research Institute, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
authors.forename: Xiangchun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Nephrology Research Institute, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Nephrology Research Institute, The Second Hospital of Shandong University, Shandong University, Jinan, People's Republic of China guangj@sdu.edu.cn.
authors.forename: Guangju
authors.initials: G
authors.lastname: Guan
mesh_terms: D000199:Actins / Q000187:drug effects / Q000235:genetics; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D029681:Arabidopsis Proteins / Q000187:drug effects* / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005353:Fibronectins; D005947:Glucose / Q000494:pharmacology*; D007150:Immunohistochemistry; D019751:Intramolecular Transferases / Q000187:drug effects* / Q000378:metabolism; D007668:Kidney / Q000473:pathology*; D008297:Male; D051379:Mice; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000187:drug effects / Q000235:genetics; D026362:Serum Response Factor / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D013549:Sweetening Agents / Q000494:pharmacology*; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000187:drug effects / Q000235:genetics
chemical_list: D000199:Actins; D000813:Anilides; D029681:Arabidopsis Proteins; D001549:Benzamides; C523455:CCG 1423; D005353:Fibronectins; C511173:Mrtfa protein, mouse; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D026362:Serum Response Factor; C000604450:Snai2 protein, rat; D000071250:Snail Family Transcription Factors; D013549:Sweetening Agents; C569043:Tjp1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D062826:Zonula Occludens-1 Protein; C544013:alpha-smooth muscle actin, mouse; D019751:Intramolecular Transferases; C568454:marneral synthase, Arabidopsis; D005947:Glucose
keywords: CCG-1423; Serum response factor; Snail; diabetic nephropathy; epithelial–mesenchymal transition; podocyte