title: The RhoA/ROCK Pathway Ameliorates Adhesion and Inflammatory Infiltration Induced by AGEs in Glomerular Endothelial Cells.
abstract: A recent study demonstrated that advanced glycation end products (AGEs) play a role in monocyte infiltration in mesangial areas in diabetic nephropathy. The Ras homolog gene family, member A Rho kinase (RhoA/ROCK) pathway plays a role in regulating cell migration. We hypothesized that the RhoA/ROCK pathway affects adhesion and inflammation in endothelial cells induced by AGEs. Rat glomerular endothelial cells (rGECs) were cultured with AGEs (80 μg/ml) in vitro. The ROCK inhibitor Y27632 (10 nmol/l) and ROCK1-siRNA were used to inhibit ROCK. We investigated levels of the intercellular adhesion molecule 1 (ICAM-1) and monocyte chemoattractant protein1 (MCP-1) in rGECs. Db/db mice were used as a diabetes model and received Fasudil (10 mg/kg/d, n = 6) via intraperitoneal injection for 12 weeks. We found that AGEs increased the expression of ICAM-1 and MCP-1 in rGECs, and the RhoA/ROCK pathway inhibitor Y27632 depressed the release of adhesion molecules. Moreover, blocking the RhoA/ROCK pathway ameliorated macrophage transfer to the endothelium. Reduced expression of adhesion molecules and amelioration of inflammatory cell infiltration in the glomerulus were observed in db/db mice treated with Fasudil. The RhoA/ROCK pathway plays a role in adhesion molecule expression and inflammatory cell infiltration in glomerular endothelial cells induced by AGEs.
authors.affiliation: Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Jialing
authors.initials: J
authors.lastname: Rao
authors.affiliation: Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Zengchun
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
authors.affiliation: Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.affiliation: Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Weiyan
authors.initials: W
authors.lastname: Lai
authors.affiliation: Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Wanbing
authors.initials: W
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Tanqi
authors.initials: T
authors.lastname: Lou
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000577:Amides / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007678:Kidney Glomerulus / Q000473:pathology*; D051379:Mice; D008817:Mice, Mutant Strains; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000577:Amides; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D017127:Glycation End Products, Advanced; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D034741:RNA, Small Interfering; D018799:Intercellular Adhesion Molecule-1; C108830:Y 27632; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C578418:ROCK1 protein, rat; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; C049347:fasudil