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DNMT3A regulates differentiation of osteoblast and autophagy of vascular smooth muscle cells in vascular medial calcification induced by high phosphorus through ERK1/2 signaling

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机构: [1]Departments of Nephrology, The Fourth Hospital of Hebei Medical University, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, Shijiazhuang, Hebei Province, P.R. China
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关键词: DNMT3A osteoblast differentiation medial vascular calcification autophagy ERK1/2

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To investigate the effect of DNMT3A in vascular calcification (VC) induced by high phosphorus. The arterial tissues of 12 patients with end stage renal disease (ESRD) and VC and 12 patients with ESRD without VC were collected. Rat vascular smooth muscle cells (VSMCs) were divided into control group, high phosphorus (P) group, P + DMSO group, p-ERK1/2 inhibitor group, DNMT3A group and DNMT3A + P group and P + shRNA-DNMT3A group. Vascular calcification was evaluated by von kossa staining. Cell calcification was evaluated by alizarin red staining. The calcium content was assessed by calcium determination kit. The levels of DNMT3A, Runx2, LC3 and p-ERK1/2 were significantly up-regulated in CKD patients with VC in comparison with those in CKD patients without VC(p<0.05). Moreover, the levels of SM22a and P62 were notably decreased in CKD patients with VC in comparison with those in CKD patients without VC(p<0.05). Similar changes were observed in VSMCs induced by high phosphorus. Knock down of DNMT3A in VSMCs inhibited phenotypic transformation and induced autophagy, then reduced calcification(p<0.05). Moreover, p-ERK1/2 level was downregulated by knock down of DNMT3A in comparison with the control group(p<0.05). In conclusion, DNMT3A regulated high phosphorus induced vascular medial calcification via ERK1/2 signaling.

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大类 | 3 区 农林科学
小类 | 4 区 食品科技
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第一作者机构: [1]Departments of Nephrology, The Fourth Hospital of Hebei Medical University, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, Shijiazhuang, Hebei Province, P.R. China
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