| 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
|
| Resource |
| Mice |
RBRC01726 |
