Table 1.
Summary of Published Findings Pertaining to ROCK in Diabetic Vascular Complications.
| Function/observation | References | |
|---|---|---|
| Nephropathy | ||
| Mesangial cells | ・Activated by glucose, TNF-α, TGF-β, angiotensin II, and VEGF | (8), (11), (16), (17), (18), (65) |
| ・ROCK inhibitor-treated diabetic mice exhibit reduced glomerular sclerosis and macrophage infiltration | ||
| ・Mediates HIF1-induced fibrotic responses (CTGF, PAI-1) | ||
| ・Regulates the expression of MCP-1 and M-CSF by controlling AP-1 and NF-κB | ||
| Podocytes | ・Activated by glucose, TGF-β, and ROS | (14), (16), (59) |
| ・ROCK inhibitor-treated diabetic rodents exhibit reduced albuminuria and apoptosis | ||
| ・Forced expression of ROCK results in albuminuria and apoptosis | ||
| ・Regulates the expression of Notch ligand and mitochondrial morphology | ||
| Glomerular endothelium | ・Activated by AGEs | (66) |
| ・Mediates permeability, morphology, and EMT | ||
| ・Regulates the expression of adhesion molecules and chemokines | ||
| Tubules | ・ROCK inhibitor-treated diabetic rats exhibit reduced interstitial fibrosis | (19), (46) |
| ・Regulates sphingosine-1-phosphate-induced EMT | ||
| Retinopathy | ||
| Pericytes | ・ROCK inhibitor reduces retinal VEGF expression in diabetic rats | (49) |
| ・Regulates PDGF-induced VEGF expression | ||
| Endothelium | ・ROCK inhibitor reduces leukocyte adhesion and the number of damaged cells in diabetic rats | |
| ・Regulates the expression of ICAM1 | ||
| Neuropathy | ||
| Myelin sheath | ・ROCK inhibitor treated diabetic rats exhibit improvement of motor nerve conduction velocity | (10) |
| ・Regulates distribution of adhesion molecules | ||
| ・Pathogenic roles in other cell types in nervous system in not determined | ||
| Large vessels | ||
| VSMC | ・Activated by static pressure, angiotensin II, thrombin, PDGF, extracellular nucleotides, and urotensin | (13), (54) |
| ・Mediates cell proliferation, migration, Ca2+ sensitization, and contraction | ||
| ・Regulates the expression of IL-6, MCP-1, MIF, ROS formation, and cyclophilin A secretion | ||
| Endothelium | ・Activated by angiotensin II, IL-1β, thrombin, ER stress, and lysophosphatidic acid | (38), (54), (56) |
| ・Mediates barrier function and permeability | ||
| ・Regulates the expression of E-selectin, MCP-1, VCAM1, NO production, NADPH oxidase activity | ||
| Inflammatory cells | ・Regulates chemotaxis and foam cells formation by inhibiting reverse cholesterol transport | (63), (67) |
TNF-α, tumor necrosis factor α; TGF-β, transforming growth factor β; VEGF, vascular endothelial growth factor; MCP-1, Monocyte chemoattractant protein 1; M-CSF, macrophage colony-stimulating factor; AP-1, activator protein 1; NF-κB, nuclear factor κB; HIF-1, hypoxia-inducible factor 1; CTGF, connective tissue growth factor; PAI-1, plasminogen activator inhibitor 1; ROS, Reactive oxygen species; AGEs, advanced glycation end products; EMT, epithelial mesenchymal transition; PDGF, platelet-derived growth factor; ICAM1, intercellular adhesion molecule 1; IL-6, interleukin 6; MIF, macrophage migration inhibitory factor; ER, endoplasmic reticulum; IL-1β, interleukin 1β; VCAM1, vascular cellular adhesion molecule 1; NO, nitric oxide; NADPH, nicotinamide adenine dinucleotide phosphate.