期刊
FASEB JOURNAL
卷 32, 期 8, 页码 4315-4327出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201701257R
关键词
smooth muscle cell; renal blood flow; endothelial cell; APJ; kidney
资金
- Natural Science Foundation of China [81270815]
The cause of the invalid reaction of smooth muscle cells to mechanical stimulation that results in a dysfunctional myogenic response that mediates the disruption of renal blood flow (RBF) in patients with diabetes is debatable. The present study revealed that increased apelin concentration in serum of diabetic mice neutralized the myogenic response mediated by apelin receptor (APJ) and resulted in increased RBF, which promoted the progression of diabetic nephropathy. The results showed that apelin concentration, RBF, and albuminuria:creatinine ratio were all increased in kkAy mice, and increased RBF correlated positively with serum apelin both in C57 and diabetic mice. The increased RBF was accompanied by decreased phosphorylation of myosin light chain (MLC), -arrestin, and increased endothelial NOS in glomeruli. Meanwhile, calcium, phosphorylation of MLC, and -arrestin were decreased by high glucose and apelin treatment in cultured smooth muscle cells, as well. eNOS was increased by high glucose and increased by apelin in cultured endothelial cells (ECs). Knockdown of -arrestin expression in smooth muscle cells cancelled phosphorylation of MLC induced by apelin. Therefore, apelin may induce the progression of diabetic nephropathy by counteracting the myogenic response in smooth muscle cells.Zhang, J., Yin, J., Wang, Y., Li, B., Zeng, X. Apelin impairs myogenic response to induce diabetic nephropathy in mice.
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