| First Author | Chiang HY | Year | 2022 |
| Journal | Commun Biol | Volume | 5 |
| Issue | 1 | Pages | 364 |
| PubMed ID | 35440618 | Mgi Jnum | J:324334 |
| Mgi Id | MGI:7265444 | Doi | 10.1038/s42003-022-03313-z |
| Citation | Chiang HY, et al. (2022) MFG-E8 promotes osteogenic transdifferentiation of smooth muscle cells and vascular calcification by regulating TGF-beta1 signaling. Commun Biol 5(1):364 |
| abstractText | Vascular calcification occurs in arterial aging, atherosclerosis, diabetes mellitus, and chronic kidney disease. Transforming growth factor-beta1 (TGF-beta1) 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-beta1-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 beta1 integrin-dependent MMP2 expression, causing TGF-beta1 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. |
