Ana Tomasovic, Nina Susanne Kurrle, Frank Wempe, Silke De-Zolt, Susan Scheibe, Katri Koli, Martin Serchinger, Frank Schnütgen, Duran Sürün, Anja Sterner-Kock, Norbert Weißmann, Harald von Melchner
- 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.
MetadatenAuthor: | Ana Tomasovic, Nina Susanne KurrleORCiDGND, Frank WempeGND, Silke De-Zolt, Susan Scheibe, Katri Koli, Martin Serchinger, Frank SchnütgenORCiDGND, Duran SürünORCiDGND, Anja Sterner-Kock, Norbert WeißmannGND, Harald von Melchner |
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URN: | urn:nbn:de:hebis:30:3-453358 |
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DOI: | https://doi.org/10.1016/j.matbio.2016.09.006 |
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ISSN: | 1569-1802 |
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ISSN: | 0945-053X |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/27645114 |
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Parent Title (English): | Matrix biology |
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Publisher: | Elsevier |
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Place of publication: | Amsterdam [u. a.] |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2016 |
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Date of first Publication: | 2016/09/17 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2018/01/16 |
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Tag: | COPD; Emphysema; Ltbp4; Nrf2; Pdgfrβ; ROS; Tgfβ |
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Volume: | 59 |
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Page Number: | 12 |
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First Page: | 109 |
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Last Page: | 120 |
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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/). |
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HeBIS-PPN: | 428728294 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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