Universität zu Köln

Tomasovic, Ana, Kurrle, Nina, Wempe, Frank, De-Zolt, Siike, Scheibe, Susan, Koli, Katri, Serchinger, Martin, Schnuetgen, Frank, Sueruen, Duran, Sterner-Kock, Anja, Weissmann, Norbert ORCID: 0000-0003-2675-3871 and von Meichner, Harald (2017). Ltbp4 regulates Pdgfr beta expression via TGF beta-dependent modulation of Nrf2 transcription factor function. Matrix Biol., 59. S. 109 - 121. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1569-1802

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tomasovic, Ana UNSPECIFIED UNSPECIFIED UNSPECIFIED Kurrle, Nina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wempe, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED De-Zolt, Siike UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheibe, Susan UNSPECIFIED UNSPECIFIED UNSPECIFIED Koli, Katri UNSPECIFIED UNSPECIFIED UNSPECIFIED Serchinger, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schnuetgen, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Sueruen, Duran UNSPECIFIED UNSPECIFIED UNSPECIFIED Sterner-Kock, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Weissmann, Norbert UNSPECIFIED orcid.org/0000-0003-2675-3871 UNSPECIFIED von Meichner, Harald UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-233003
DOI:	10.1016/j.matbio.2016.09.006
Journal or Publication Title:	Matrix Biol.
Volume:	59
Page Range:	S. 109 - 121
Date:	2017
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1569-1802
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GROWTH-FACTOR-BETA; OBSTRUCTIVE PULMONARY-DISEASE; SMOOTH-MUSCLE-CELLS; C-MYC; ACTIVATION; BINDING; FIBROBLASTS; RECEPTOR; LUNG; TRANSFORMING-GROWTH-FACTOR-BETA-1 Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23300