RRC ID 70353
Author Chiang HY, Chu PH, Chen SC, Lee TH.
Title MFG-E8 promotes osteogenic transdifferentiation of smooth muscle cells and vascular calcification by regulating TGF-β1 signaling.
Journal Commun Biol
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 and phenotypic transformation to osteoblast-like cells in response to osteogenic medium. MFG-E8 promotes β1 integrin-dependent MMP2 expression, causing TGF-β1 activation and subsequent VSMC osteogenic transdifferentiation and biomineralization. Thus, the established molecular link between MFG-E8 and vascular calcification suggests that MFG-E8 can be therapeutically targeted to mitigate vascular calcification.
Volume 5(1)
Pages 364
Published 2022-4-19
DOI 10.1038/s42003-022-03313-z
PII 10.1038/s42003-022-03313-z
PMID 35440618
PMC PMC9018696
MeSH Aged Antigens, Surface / genetics Antigens, Surface / metabolism Cell Transdifferentiation Factor VIII / metabolism Glycolipids Glycoproteins / metabolism Humans Lipid Droplets Milk Proteins / genetics Milk Proteins / metabolism Myocytes, Smooth Muscle / metabolism Transforming Growth Factor beta1* / metabolism Vascular Calcification* / metabolism
IF 4.165
Mice RBRC01726