Lethal giant larvae 1 inhibits smooth muscle calcification via high mobility group box 1.
Lethal giant larvae 1 inhibits smooth muscle calcification via high mobility group box 1.
复制标题
致命的巨型幼虫 1 通过高迁移率组盒 1 抑制平滑肌钙化。
DOI：
10.1016/j.yjmcc.2020.03.017
复制
发表时间：
2020-04
期刊：
影响因子：
--
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Zhang T;Cao G;Meng X;Ouyang C;Gao J;Sun Y;Wu J;Min Q;Zhang C;Zhang W
血管钙化是与动脉粥样硬化、糖尿病性血管疾病、血管损伤、高血压、慢性肾脏疾病和衰老密切相关的病理过程。致死性巨幼虫1（Lethal giant larvae 1，LGL 1）是细胞极性的关键调节因子，在肿瘤发生中起重要作用。然而，LGL 1是否调节血管钙化仍不清楚。在这项研究中，我们通过将LGL 1flox/plant小鼠与α-SMA-Cre小鼠杂交产生平滑肌特异性LGL 1敲除（LGL 1 SMKO）小鼠。在钙化条件下，LGL 1水平显著降低。LGL 1过表达抑制高磷诱导的血管平滑肌细胞钙化。机械上，LGL 1可与高迁移率族蛋白1（HMGB 1）结合，通过溶酶体途径促进其降解，从而抑制钙化。平滑肌特异性LGL 1缺失增加了HMGB 1水平，加重了维生素D3诱导的血管钙化，HMGB 1抑制剂可减弱血管钙化。LGL 1可能通过促进HMGB 1降解而抑制成骨分化，从而抑制血管钙化。
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/floxmice 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 degradationviathe 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 differentiationviapromoting HMGB1 degradation.
登录
查看更多内容
影响因子：
2.9
作者：
Rennenberg RJ;Kessels AG;Schurgers LJ;van Engelshoven JM;de Leeuw PW;Kroon AA
通讯作者：
Kroon AA
影响因子：
9.3
作者：
Leopold JA
通讯作者：
Leopold JA
影响因子：
64.8
作者：
Scaffidi, P;Misteli, T;Bianchi, ME
通讯作者：
Bianchi, ME
影响因子：
21.3
作者：
Plant, PJ;Fawcett, JP;Pawson, T
通讯作者：
Pawson, T
影响因子：
37.8
作者：
Shroff, Rukshana C.;McNair, Rosamund;Shanahan, Catherine M.
通讯作者：
Shanahan, Catherine M.