血管平滑肌
Wnt信号通路
钙化
基因敲除
细胞生物学
癌症研究
化学
信号转导
内分泌学
内科学
生物
医学
生物化学
细胞凋亡
平滑肌
作者
Beidong Chen,Yang Zhao,Duanyang Han,Ban Zhao,Yonghui Mao,Zhong‐Kai Cui,Yun-Chin Chu,Lu Feng,Sen Yin,Cun‐Yu Wang,Xian Wang,Ming‐Jiang Xu,Gexin Zhao
标识
DOI:10.1016/j.yjmcc.2019.07.008
摘要
Abstract
Aims
Wnt signaling plays a critical role in vascular calcification (VC). Wnt factors induce different physiological and pathological effects on cardiovascular functions. Wnt1, a ligand of Wnt/β-catenin signaling, promotes pro-angiogenesis and reduces myocardial infarction. The role of Wnt1 on VC in chronic kidney disease (CKD) is not fully understood. Methods and results
We used human vascular smooth muscle cells (VSMCs) and a rat model of chronic renal failure (CRF), and observed a native protective mechanism by which VC is reduced via the activation of Wnt1 and its transcriptional target ANKH inorganic pyrophosphate transport regulator (ANKH) gene. ANKH is an essential calcification inhibitor that effluxes inorganic pyrophosphate (PPi) from VSMCs to play an inhibitory role in VC. Vascular ANKH and plasma PPi were significantly downregulated in the rat model of CRF. The knockdown or inhibition of ANKH reversed the effect of Wnt1 on VC in VSMCs. Clinical analysis revealed low plasma levels of Wnt1 and PPi were associated with CKD in patients. Applying a Wnt/β-catenin signaling agonist can alleviate the progression of VC. Conclusion
This work reveals the ANKH regulation of Wnt1 in VSMCs is essential for blocking VC. Our findings may contribute to the development of medications that target Wnt signaling and/or ANKH to inhibit VC.
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