title: Long-term diabetic complications may be ameliorated by targeting Rho kinase.
abstract: This review addresses the roles of Rho/Rho-kinase (ROCK) pathway in the pathogenesis of diabetes complications. Diabetes can cause many serious complications and can result in physical disability or even increased mortality. However, there are not many effective ways to treat these complications. The small guanosine-5'-triphosphate-binding protein Rho and its downstream target Rho-kinase mediate important cellular functions, such as cell morphology, motility, secretion, proliferation, and gene expression. Recently, the Rho/Rho-kinase pathway has attracted a great deal of attention in diabetes-related research. These studies have provided evidence that the activity and gene expression of Rho-kinase are upregulated in some tissues in animal models of type 1 or type 2 diabetes and in cell lines cultured with high concentrations of glucose. Inhibitors of Rho-kinase could prevent or ameliorate the pathological changes in diabetic complications. The inhibitory effects of statins on the Rho/Rho-kinase signalling pathway may also play a role in the prevention of diabetic complications. However, the precise molecular mechanism by which the Rho/Roh-kinase pathway participates in the development or progression of diabetic complications has not been extensively investigated. This article evaluates the relationship between Rho/Roh-kinase activation and diabetic complications, as well as the roles of Roh-kinase inhibitors and statins in the complications of diabetes, with the objective of providing a novel target for the treatment of long-term diabetic complications.
authors.affiliation: Department of Endocrinology, The Second Hospital of He Bei Medical University, Shijiazhuang, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D048909:Diabetes Complications / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047428:Protein Kinase Inhibitors; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins