MFG-E8 promotes osteogenic transdifferentiation of smooth muscle cells and vascular calcification by regulating TGF-β1 signaling.

ABSTRACT: Vascular calcification occurs in arterial aging, atherosclerosis, diabetes mellitus, and chronic kidney disease. Transforming growth factor-β1 (TGF-β1) is a key modulator driving the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs), leading to vascular calcification. We hypothesize that milk fat globule-epidermal growth factor 8 (MFG-E8), a glycoprotein expressed in VSMCs, promotes the osteogenic transdifferentiation of VSMCs through the activation of TGF-β1-mediated signaling. We observe that the genetic deletion of MFG-E8 prevents calcium chloride-induced vascular calcification in common carotid arteries (CCAs). The exogenous application of MFG-E8 to aged CCAs promotes arterial wall calcification. MFG-E8-deficient cultured VSMCs exhibit decreased biomineralization

SUBMITTER: Chiang HY 

PROVIDER: S-EPMC9018696 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature