| First Author | Calvier L | Year | 2017 |
| Journal | Cell Metab | Volume | 25 |
| Issue | 5 | Pages | 1118-1134.e7 |
| PubMed ID | 28467929 | Mgi Jnum | J:253285 |
| Mgi Id | MGI:6106785 | Doi | 10.1016/j.cmet.2017.03.011 |
| Citation | Calvier L, et al. (2017) PPARgamma Links BMP2 and TGFbeta1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism. Cell Metab 25(5):1118-1134.e7 |
| abstractText | BMP2 and TGFbeta1 are functional antagonists of pathological remodeling in the arteries, heart, and lung; however, the mechanisms in VSMCs, and their disturbance in pulmonary arterial hypertension (PAH), are unclear. We found a pro-proliferative TGFbeta1-Stat3-FoxO1 axis in VSMCs, and PPARgamma as inhibitory regulator of TGFbeta1-Stat3-FoxO1 and TGFbeta1-Smad3/4, by physically interacting with Stat3 and Smad3. TGFbeta1 induces fibrosis-related genes and miR-130a/301b, suppressing PPARgamma. Conversely, PPARgamma inhibits TGFbeta1-induced mitochondrial activation and VSMC proliferation, and regulates two glucose metabolism-related enzymes, platelet isoform of phosphofructokinase (PFKP, a PPARgamma target, via miR-331-5p) and protein phosphatase 1 regulatory subunit 3G (PPP1R3G, a Smad3 target). PPARgamma knockdown/deletion in VSMCs activates TGFbeta1 signaling. The PPARgamma agonist pioglitazone reverses PAH and inhibits the TGFbeta1-Stat3-FoxO1 axis in TGFbeta1-overexpressing mice. We identified PPARgamma as a missing link between BMP2 and TGFbeta1 pathways in VSMCs. PPARgamma activation can be beneficial in TGFbeta1-associated diseases, such as PAH, parenchymal lung diseases, and Marfan's syndrome. |
