Reference - Detail
| 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC01726 |