The Calcimimetic R568 Reduces Vascular Smooth Muscle Cell Calcification in Vitro Via ERK 1/2 Phosphorylation.

IF 1.7 Q3 UROLOGY & NEPHROLOGY
International Journal of Nephrology Pub Date : 2025-03-18 eCollection Date: 2025-01-01 DOI:10.1155/ijne/2492846
Jonas Engeßer, Philipp Gregor Albert, Matthias Scheuch, Norina Loth, Sylvia Stracke
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引用次数: 0

Abstract

Background: Vascular calcification (VC) is a common complication of chronic kidney disease, ultimately leading to high morbidity and cardiovascular mortality. In this study, we investigated the effects of the calcimimetic R568 in an in vitro model of human vascular smooth muscle cell (VSMC) calcification. Methods: Human VSMCs were cultured under elevated calcium (2.4 mmol/L) and phosphate (2.7 mmol/L) concentrations. Calcification was analyzed using von Kossa staining and colorimetric calcium measurement. Intracellular signaling was examined via Western blot, and apoptosis was assessed by the TUNEL assay. Results: Treatment with R568 significantly reduced VC over the 9-day treatment period. R568 treatment led to increased phosphorylation of extracellular signal-regulated kinase (ERK 1/2) compared to the control group. Calcimimetic treatment was also associated with a reduction in apoptosis. Blocking ERK 1/2 phosphorylation completely abolished the inhibitory effects of R568 on VC. Conclusion: Our study provides new insights into the mechanism of action of calcimimetics during VC and highlights the importance of ERK 1/2 signaling in this process.

拟钙化物R568通过ERK 1/2磷酸化减少血管平滑肌细胞钙化。
背景:血管钙化(VC)是慢性肾脏疾病的常见并发症,最终导致高发病率和心血管死亡率。本研究探讨了拟钙化剂R568对体外人血管平滑肌细胞(VSMC)钙化的影响。方法:在升高钙(2.4 mmol/L)和磷酸(2.7 mmol/L)浓度下培养人VSMCs。采用von Kossa染色和比色钙法分析钙化情况。Western blot检测细胞内信号传导,TUNEL法检测细胞凋亡。结果:R568在9天的治疗期内显著降低了VC。与对照组相比,R568处理导致细胞外信号调节激酶(ERK 1/2)磷酸化增加。石灰化处理也与细胞凋亡的减少有关。阻断ERK 1/2磷酸化完全消除R568对VC的抑制作用。结论:我们的研究为钙化剂在VC中的作用机制提供了新的见解,并强调了erk1 /2信号在这一过程中的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International Journal of Nephrology
International Journal of Nephrology UROLOGY & NEPHROLOGY-
CiteScore
3.40
自引率
4.80%
发文量
44
审稿时长
17 weeks
期刊介绍: International Journal of Nephrology is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies focusing on the prevention, diagnosis, and management of kidney diseases and associated disorders. The journal welcomes submissions related to cell biology, developmental biology, genetics, immunology, pathology, pathophysiology of renal disease and progression, clinical nephrology, dialysis, and transplantation.
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