TY  - JOUR
A1  - Tomasovic, Ana
A1  - Kurrle, Nina Susanne
A1  - Wempe, Frank
A1  - De-Zolt, Silke
A1  - Scheibe, Susan
A1  - Koli, Katri
A1  - Serchinger, Martin
A1  - Schnütgen, Frank
A1  - Sürün, Duran
A1  - Sterner-Kock, Anja
A1  - Weißmann, Norbert
A1  - Melchner, Harald von
T1  - Ltbp4 regulates Pdgfrβ expression via TGFβ-dependent modulation of Nrf2 transcription factor function
T2  - Matrix biology
N2  - 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.
KW  - Ltbp4
KW  - Tgfβ
KW  - Pdgfrβ
KW  - Nrf2
KW  - ROS
KW  - Emphysema
KW  - COPD
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45335
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-453358
SN  - 1569-1802
SN  - 0945-053X
N1  - © 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/).
VL  - 59
SP  - 109
EP  - 120
PB  - Elsevier
CY  - Amsterdam [u. a.]
ER  -