| First Author | Zhang T | Year | 2020 |
| Journal | J Mol Cell Cardiol | Volume | 142 |
| Pages | 39-52 | PubMed ID | 32268148 |
| Mgi Jnum | J:296923 | Mgi Id | MGI:6441582 |
| Doi | 10.1016/j.yjmcc.2020.03.017 | Citation | Zhang T, et al. (2020) Lethal giant larvae 1 inhibits smooth muscle calcification via high mobility group box 1. J Mol Cell Cardiol 142:39-52 |
| abstractText | 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 (LGL1(SMKO)) mice by cross-breeding LGL1(flox/flox) mice with alpha-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. |
