Ltbp4 regulates Pdgfr beta expression via TGF beta-dependent modulation of Nrf2 transcription factor function

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http://hdl.handle.net/10138/195373

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Tomasovic , A , Kurrle , N , Wempe , F , De-Zolt , S , Scheibe , S , Koli , K , Serchinger , M , Schnuetgen , F , Sueruen , D , Sterner-Kock , A , Weissmann , N & von Meichner , H 2017 , ' Ltbp4 regulates Pdgfr beta expression via TGF beta-dependent modulation of Nrf2 transcription factor function ' , Matrix Biology , vol. 59 , pp. 109-120 . https://doi.org/10.1016/j.matbio.2016.09.006

Title: Ltbp4 regulates Pdgfr beta expression via TGF beta-dependent modulation of Nrf2 transcription factor function
Author: Tomasovic, Ana; Kurrle, Nina; Wempe, Frank; De-Zolt, Siike; Scheibe, Susan; Koli, Katri; Serchinger, Martin; Schnuetgen, Frank; Sueruen, Duran; Sterner-Kock, Anja; Weissmann, Norbert; von Meichner, Harald
Contributor: University of Helsinki, Research Programs Unit
Date: 2017-05
Language: eng
Number of pages: 12
Belongs to series: Matrix Biology
ISSN: 0945-053X
URI: http://hdl.handle.net/10138/195373
Abstract: 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 TGF beta 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 Pdgfr beta-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 Pdgfr beta signaling. Here we show that LTBP4 induces Pdgfr beta signaling by inhibiting the antioxidant Nr12/Keap1 pathway in a TGF beta-dependent manner. Overall, our data identified Ltbp4 as a major player in lung remodeling and injury repair. (C) 2016 The Authors. Published by Elsevier B.V.
Subject: Ltbp4
Tgf beta
Pdgfr beta
Nrf2
ROS
Emphysema
GROWTH-FACTOR-BETA
OBSTRUCTIVE PULMONARY-DISEASE
SMOOTH-MUSCLE-CELLS
C-MYC
ACTIVATION
BINDING
FIBROBLASTS
RECEPTOR
LUNG
TRANSFORMING-GROWTH-FACTOR-BETA-1
3111 Biomedicine
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