From: ROCK Inhibition May Stop Diabetic Kidney Disease
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) |