| First Author | Liang Q | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 25785 | PubMed ID | 27173636 |
| Mgi Jnum | J:272289 | Mgi Id | MGI:6216578 |
| Doi | 10.1038/srep25785 | Citation | Liang Q, et al. (2016) Identification of P-Rex1 as an anti-inflammatory and anti-fibrogenic target for pulmonary fibrosis. Sci Rep 6:25785 |
| abstractText | Pulmonary fibrosis (PF) leads to progressive and often irreversible loss of lung functions, posing a health threat with no effective cure. We examined P-Rex1, a PI3K- and G protein betagamma-regulated guanine nucleotide exchange factor (GEF) of the Rac small GTPase, for its potential involvement in PF. In a bleomycin-induced PF model, mice deficient in p-rex1 had well-preserved alveolar structure and survived significantly better than their wild type (WT) littermates. The p-rex1(-/-) mice expressed significantly less proinflammatory cytokines and chemokines and had reduced leukocyte infiltration in the lung tissue than their WT littermates. P-Rex1 was detected in lung fibroblasts of WT mice, and its genetic deletion attenuated TGFbeta-1-stimulated lung fibroblast migration, Rac1 activation and p38 MAPK phosphorylation. The p-rex1(-/-) mice showed significantly reduced pathological changes including the expression of alpha-smooth muscle actin, fibronectin and TGFbeta-1 compared with their WT controls. Expression of a GEF-deficient P-Rex1 mutant effectively blocked Smads-dependent transcriptional activation, suggesting that P-Rex1 is a downstream mediator of TGFbeta-1 signaling. These findings identify P-Rex1 as a novel player of PF, suggesting that targeting P-Rex1 may simultaneously block the inflammatory and fibrogenic processes of PF. |
