Ltbp4 regulates Pdgfrβ expression via TGFβ-dependent modulation of Nrf2 transcription factor function

  • 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 −/−) 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 −/− 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.
Metadaten
Author:Ana Tomasovic, Nina Susanne KurrleORCiDGND, Frank Wempe, Silke De-Zolt, Susan Scheibe, Katri Koli, Martin Serchinger, Frank SchnütgenORCiDGND, Duran Sürün, Anja Sterner-Kock, Norbert Weißmann, Harald von Melchner
URN:urn:nbn:de:hebis:30:3-453358
DOI:https://doi.org/10.1016/j.matbio.2016.09.006
ISSN:1569-1802
ISSN:0945-053X
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/27645114
Parent Title (English):Matrix biology
Publisher:Elsevier
Place of publication:Amsterdam [u. a.]
Document Type:Article
Language:English
Year of Completion:2016
Date of first Publication:2016/09/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/01/16
Tag:COPD; Emphysema; Ltbp4; Nrf2; Pdgfrβ; ROS; Tgfβ
Volume:59
Page Number:12
First Page:109
Last Page:120
Note:
© 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
HeBIS-PPN:428728294
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0