| First Author | Ohno S | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 27192 | PubMed ID | 27273361 |
| Mgi Jnum | J:266752 | Mgi Id | MGI:6216725 |
| Doi | 10.1038/srep27192 | Citation | Ohno S, et al. (2016) Ablation of the N-type calcium channel ameliorates diabetic nephropathy with improved glycemic control and reduced blood pressure. Sci Rep 6:27192 |
| abstractText | Pharmacological blockade of the N- and L-type calcium channel lessens renal injury in kidney disease patients. The significance of specific blockade of alpha1 subunit of N-type calcium channel, Cav2.2, in diabetic nephropathy, however, remains to be clarified. To examine functional roles, we mated Cav2.2(-/-) mice with db/db (diabetic) mice on the C57BLKS background. Cav2.2 was localized in glomeruli including podocytes and in distal tubular cells. Diabetic Cav2.2(-/-) mice significantly reduced urinary albumin excretion, glomerular hyperfiltration, blood glucose levels, histological deterioration and systolic blood pressure (SBP) with decreased urinary catecholamine compared to diabetic Cav2.2(+/+) mice. Interestingly, diabetic heterozygous Cav2.2(+/-) mice also decreased albuminuria, although they exhibited comparable systolic blood pressure, sympathetic nerve activity and creatinine clearance to diabetic Cav2.2(+/+) mice. Consistently, diabetic mice with cilnidipine, an N-/L-type calcium channel blocker, showed a reduction in albuminuria and improvement of glomerular changes compared to diabetic mice with nitrendipine. In cultured podocytes, depolarization-dependent calcium responses were decreased by omega-conotoxin, a Cav2.2-specific inhibitor. Furthermore, reduction of nephrin by transforming growth factor-beta (TGF-beta) in podocytes was abolished with omega-conotoxin, cilnidipine or mitogen-activated protein kinase kinase inhibitor. In conclusion, Cav2.2 inhibition exerts renoprotective effects against the progression of diabetic nephropathy, partly by protecting podocytes. |
