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Lethal giant larvae 1 inhibits smooth muscle calcification via high mobility group box 1.
Journal of Molecular and Cellular Cardiology ( IF 5 ) Pub Date : 2020-04-05 , DOI: 10.1016/j.yjmcc.2020.03.017
Tianran Zhang 1 , Guangqing Cao 2 , Xiao Meng 1 , Changhan Ouyang 3 , Jiangang Gao 4 , Yuanyuan Sun 1 , Jiliang Wu 3 , Qing Min 3 , Cheng Zhang 1 , Wencheng Zhang 5
Affiliation  

Vascular calcification is a pathological process closely related to atherosclerosis, diabetic vascular diseases, vascular injury, hypertension, chronic kidney disease and aging. Lethal giant larvae 1 (LGL1) is known as a key regulator of cell polarity and plays an important role in tumorigenesis. However, whether LGL1 regulates vascular calcification remains unclear. In this study, we generated smooth muscle-specific LGL1 knockout (LGL1SMKO) mice by cross-breeding LGL1flox/flox mice with α-SMA-Cre mice. LGL1 level was significantly decreased during calcifying conditions. Overexpression of LGL1 restrained high phosphate-induced calcification in vascular smooth muscle cells (VSMCs). Mechanically, LGL1 could bind with high mobility group box 1 (HMGB1) and promote its degradation via the lysosomal pathway, thereby inhibiting calcification. Smooth muscle-specific deletion of LGL1 increased HMGB1 level and aggravated vitamin D3-induced vascular calcification, which was attenuated by an HMGB1 inhibitor. LGL1 may inhibit vascular calcification by preventing osteogenic differentiation via promoting HMGB1 degradation.

中文翻译:

致命的巨型幼虫 1 通过高迁移率群框 1 抑制平滑肌钙化。

血管钙化是与动脉粥样硬化、糖尿病血管疾病、血管损伤、高血压、慢性肾病和衰老等密切相关的病理过程。致死巨幼虫 1 (LGL1) 被认为是细胞极性的关键调节因子,在肿瘤发生中起着重要作用。然而,LGL1 是否调节血管钙化仍不清楚。在这项研究中,我们通过将 LGL1flox/flox 小鼠与 α-SMA-Cre 小鼠杂交,产生了平滑肌特异性 LGL1 敲除 (LGL1SMKO) 小鼠。LGL1 水平在钙化条件下显着降低。LGL1 的过表达抑制了血管平滑肌细胞 (VSMC) 中高磷酸盐诱导的钙化。在机械上,LGL1 可以与高迁移率族框 1 (HMGB1) 结合并通过溶酶体途径促进其降解,从而抑制钙化。LGL1 的平滑肌特异性缺失增加了 HMGB1 水平并加重了维生素 D3 诱导的血管钙化,这被 HMGB1 抑制剂减弱。LGL1 可能通过促进 HMGB1 降解来阻止成骨分化,从而抑制血管钙化。
更新日期:2020-04-06
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