| First Author | Vattulainen-Collanus S | Year | 2016 |
| Journal | J Cell Sci | Volume | 129 |
| Issue | 4 | Pages | 693-705 |
| PubMed ID | 26743080 | Mgi Jnum | J:246654 |
| Mgi Id | MGI:5923719 | Doi | 10.1242/jcs.169011 |
| Citation | Vattulainen-Collanus S, et al. (2016) Loss of PPARgamma in endothelial cells leads to impaired angiogenesis. J Cell Sci 129(4):693-705 |
| abstractText | Tie2-promoter-mediated loss of peroxisome proliferator-activated receptor gamma (PPARgamma, also known as PPARG) in mice leads to osteopetrosis and pulmonary arterial hypertension. Vascular disease is associated with loss of PPARgamma in pulmonary microvascular endothelial cells (PMVEC); we evaluated the role of PPARgamma in PMVEC functions, such as angiogenesis and migration. The role of PPARgamma in angiogenesis was evaluated in Tie2CrePPARgamma(flox/flox) and wild-type mice, and in mouse and human PMVECs. RNA sequencing and bioinformatic approaches were utilized to reveal angiogenesis-associated targets for PPARgamma. Tie2CrePPARgamma(flox/flox) mice showed an impaired angiogenic capacity. Analysis of endothelial progenitor-like cells using bone marrow transplantation combined with evaluation of isolated PMVECs revealed that loss of PPARgamma attenuates the migration and angiogenic capacity of mature PMVECs. PPARgamma-deficient human PMVECs showed a similar migration defect in culture. Bioinformatic and experimental analyses newly revealed E2F1 as a target of PPARgamma in the regulation of PMVEC migration. Disruption of the PPARgamma-E2F1 axis was associated with a dysregulated Wnt pathway related to the GSK3B interacting protein (GSKIP). In conclusion, PPARgamma plays an important role in sustaining angiogenic potential in mature PMVECs through E2F1-mediated gene regulation. |
