| First Author | Tomasovic A | Year | 2017 |
| Journal | Matrix Biol | Volume | 59 |
| Pages | 109-120 | PubMed ID | 27645114 |
| Mgi Jnum | J:253348 | Mgi Id | MGI:6092587 |
| Doi | 10.1016/j.matbio.2016.09.006 | Citation | Tomasovic A, et al. (2017) Ltbp4 regulates Pdgfrbeta expression via TGFbeta-dependent modulation of Nrf2 transcription factor function. Matrix Biol 59:109-120 |
| abstractText | Latent transforming growth factor beta binding protein 4 (LTBP4) belongs to the fibrillin/LTBP family of proteins and plays an important role as a structural component of extracellular matrix (ECM) and local regulator of TGFbeta signaling. We have previously reported that Ltbp4S knock out mice (Ltbp4S-/-) develop centrilobular emphysema reminiscent of late stage COPD, which could be partially rescued by inactivating the antioxidant protein Sestrin 2 (Sesn2). More recent studies showed that Sesn2 knock out mice upregulate Pdgfrbeta-controlled alveolar maintenance programs that protect against cigarette smoke induced pulmonary emphysema. Based on this, we hypothesized that the emphysema of Ltbp4S-/- mice is primarily caused by defective Pdgfrbeta signaling. Here we show that LTBP4 induces Pdgfrbeta signaling by inhibiting the antioxidant Nrf2/Keap1 pathway in a TGFbeta-dependent manner. Overall, our data identified Ltbp4 as a major player in lung remodeling and injury repair. |
