Loss of PKCa increases arterial medial calcification in a uremic mouse model of chronic kidney disease
Loss of PKCa increases arterial medial calcification in a uremic mouse model of chronic kidney disease
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PKCa 缺失会增加慢性肾病尿毒症小鼠模型中的动脉内侧钙化
DOI：
10.1101/2020.05.20.097642
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Borland S
中科院分区：
文献类型：
--
作者：
Borland S
Arterial medial calcification is an independent risk factor for mortality in chronic kidney disease. We previously reported that knock-down of PKCα expression increases high phosphate-induced mineral deposition by vascular smooth muscle cellsin vitro. This new study tests the hypothesis that PKCα regulates uremia-induced medial calcificationin vivo. Female wild-type and PKCα−/−mice underwent a two-stage subtotal nephrectomy and were fed a high phosphate diet for 8 weeks. X-ray micro computed tomography demonstrated that uremia-induced medial calcification was increased in the abdominal aorta and aortic arch of PKCα−/−mice compared to wild-types. Blood urea nitrogen was also increased in PKCα−/−mice compared to wild-types; there was no correlation between blood urea nitrogen and calcification in PKCα−/−mice. Phosphorylated SMAD2 immunostaining was detected in calcified aortic arches from uremic PKCα−/−mice; the osteogenic marker Runx2 was also detected in these areas. No phosphorylated SMAD2 staining were detected in calcified arches from uremic wild-types. PKCα knock-down increased TGF-β1-induced SMAD2 phosphorylation in vascular smooth muscle cellsin vitro, whereas the PKCα activator prostratin decreased SMAD2 phosphorylation. In conclusion, loss of PKCα increases uremia-induced medial calcification. The PKCα/TGF-β signaling axis could therefore represent a new therapeutic target for arterial medial calcification in chronic kidney disease.
