Lethal giant larvae 1 inhibits smooth muscle calcification via high mobility group box 1
| Autor: | Jiangang Gao, Cheng Zhang, Chang-Han Ouyang, Yuanyuan Sun, Qing Min, Guangqing Cao, Wencheng Zhang, Xiao Meng, Jiliang Wu, Tianran Zhang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Vascular smooth muscle Myocytes Smooth Muscle Regulator Gene Expression 030204 cardiovascular system & hematology medicine.disease_cause HMGB1 Muscle Smooth Vascular Mice 03 medical and health sciences 0302 clinical medicine Cell polarity medicine Animals Humans HMGB1 Protein Vitamin D Molecular Biology Cells Cultured Glycoproteins Mice Knockout biology Chemistry Calcinosis Atherosclerosis medicine.disease Immunohistochemistry Cell biology RUNX2 Disease Models Animal 030104 developmental biology biology.protein Cardiology and Cardiovascular Medicine Carcinogenesis Biomarkers Protein Binding Calcification Kidney disease |
| Zdroj: | Journal of Molecular and Cellular Cardiology. 142:39-52 |
| ISSN: | 0022-2828 |
| DOI: | 10.1016/j.yjmcc.2020.03.017 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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