Ubiquitin-specific protease 47 is associated with vascular calcification in chronic kidney disease by regulating osteogenic transdifferentiation of vascular smooth muscle cells.
Ubiquitin-specific protease 47 is associated with vascular calcification in chronic kidney disease by regulating osteogenic transdifferentiation of vascular smooth muscle cells.
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泛素特异性蛋白酶47通过调节血管平滑肌细胞的成骨转分化，与慢性肾脏疾病中的血管钙化有关。
DOI：
10.1080/0886022x.2022.2072337
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发表时间：
2022-12
期刊：
影响因子：
3
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慢性肾脏疾病（CKD）近年来已成为一个严重的健康和社会问题。血管钙化是CKD的常见并发症，是增加CKD患者心血管事件发生率和死亡率的危险因素。然而，目前还没有有效的治疗靶点，可以促进CKD血管钙化的治疗，而且副作用更小。为了确定潜在的治疗靶点，我们采用纳米uplc - MS/MS对高磷处理后的大鼠主动脉血管平滑肌细胞（RASMCs）蛋白样品进行了无标记定量（LFQ）分析。我们确定泛素特异性蛋白酶47 （USP47）可能通过调节血管平滑肌细胞（VSMC）表型的成骨转分化与CKD血管钙化有关，从而提示了CKD血管钙化的一种新的和潜在有效的治疗靶点。USP47敲低显著降低了高磷处理后RASMCs中β-转导蛋白重复序列蛋白（BTRC）、丝氨酸/苏氨酸蛋白激酶akt-1 （AKT1）、Klotho、成纤维细胞生长因子（FGF23）和基质Gla蛋白（MGP）的表达。与蛋白-蛋白相互作用（PPI）分析结果一致，USP47可能通过BTRC/AKT1途径参与CKD血管钙化过程中成骨转分化标志物的调控，如RUNX2、Klotho、FGF23和MGP。这些数据表明，USP47可能通过调节VSMCs的成骨分化与CKD的血管钙化有关。USP47可能通过涉及BTRC/AKT1途径的过程调节CKD血管钙化时VSMCs的成骨转分化。本研究确定了一种治疗慢性肾病血管钙化的新的潜在治疗靶点。
Chronic kidney disease (CKD) has recently become a serious health and social concern. Vascular calcification, a common complication of CKD, is a risk factor that increases the incidence and mortality of cardiovascular events in patients with CKD. However, there are currently no effective therapeutic targets that can facilitate treatment with fewer side effects for vascular calcification in CKD. To identify potential therapeutic targets, we performed label-free quantification (LFQ) analyses of protein samples from rat aortic vascular smooth muscle cells (RASMCs) after high-phosphorus treatment by nano-UPLC–MS/MS. We determined that ubiquitin-specific protease 47 (USP47) may be associated with CKD vascular calcification by regulating the osteogenic transdifferentiation of the vascular smooth muscle cell (VSMC) phenotype, thus suggesting a novel and potentially effective therapeutic target for CKD vascular calcification. USP47 knockdown significantly reduced the expression of β-transducin repeat-containing protein (BTRC), serine/threonine-protein kinase akt-1 (AKT1), Klotho, fibroblast growth factor (FGF23), and matrix Gla protein (MGP) in RASMCs after high-phosphorus treatment. Consistent with the results of protein–protein interaction (PPI) analyses, USP47 may be involved in regulating osteogenic transdifferentiation markers, such as runt-related transcription factor 2 (RUNX2), Klotho, FGF23, and MGP through the BTRC/AKT1 pathway upon CKD vascular calcification. These data indicate that USP47 may be associated with vascular calcification in CKD by regulating osteogenic differentiation of VSMCs. USP47 may regulate osteogenic transdifferentiation in VSMCs upon CKD vascular calcification through a process involving the BTRC/AKT1 pathway. This study identified a novel potential therapeutic target for the treatment of vascular calcification in CKD.