کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5528511 | 1548002 | 2017 | 12 صفحه PDF | دانلود رایگان |
- Ltbp4S knock out mice develop centrilobular emphysema reminiscent of late stage COPD.
- Ltbp4S induces Pdgfrβ signaling by inhibiting the antioxidant Nrf2/Keap1 pathway in a TGFβ-dependent manner.
- Pdgfrβ promotes lung regeneration and injury repair
- Loss of Ltbp4 upregulates the Sesn2/PDGFRβ suppressor pathway which is overexpressed in lungs of individuals with COPD
- As a major player in lung remodeling, Ltbp4S is likely involved in the pathogenesis of COPD.
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 TGFβ signaling. We have previously reported that Ltbp4S knock out mice (Ltbp4S â/â) 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 Pdgfrβ-controlled alveolar maintenance programs that protect against cigarette smoke induced pulmonary emphysema. Based on this, we hypothesized that the emphysema of Ltbp4S â/â mice is primarily caused by defective Pdgfrβ signaling. Here we show that LTBP4 induces Pdgfrβ signaling by inhibiting the antioxidant Nrf2/Keap1 pathway in a TGFβ-dependent manner. Overall, our data identified Ltbp4 as a major player in lung remodeling and injury repair.
Journal: Matrix Biology - Volume 59, May 2017, Pages 109-120