Pneumologie 2017; 71(S 01): S1-S125
DOI: 10.1055/s-0037-1598368
Posterbegehung – Sektion Zellbiologie
Pneumologische Grundlagenforschung – Christoph Beisswenger/Homburg (Saar), Malgorzata Wygrecka/Gießen
Georg Thieme Verlag KG Stuttgart · New York

Low density lipoprotein receptor-related protein 1deficiency exacerbates pulmonary fibrosis

M Wygrecka
1  Department of Biochemistry, Universities of Gießen and Marburg Lung Center
,
L Wujak
1  Department of Biochemistry, Universities of Gießen and Marburg Lung Center
,
I Henneke
2  Medizinische Klinik II, University of Gießen Lung Center (Uglc)
,
D Kosanovic
3  University of Gießen Lung Center
,
G Kwapiszewska
4  Ludwig Boltzmann Institute for Lung Vascular Research Graz
,
R Schermuly
5  Excellence Cluster Cardiopulmonary System, University of Gießen Lung Center
,
P Markart
6  Universitätsklinikum Gießen und Marburg GmbH
› Author Affiliations
Further Information

Publication History

Publication Date:
23 February 2017 (online)

 

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by injury and activation of alveolar epithelial cells, (myo)-fibroblast proliferation with formation of fibroblast foci, and excessive deposition of extracellular matrix (ECM) proteins. Low density lipoprotein receptor-related protein 1 (LRP1) was previously found to control cell growth and ECM turnover, however its role in the pathogenesis of IPF has not yet been described. Here, we demonstrate reduction of LRP1 expression in microdissected septae and primary lung fibroblasts isolated from IPF patients. Downregulation of LRP-1 expression was also observed in the lungs of mice subjected to the bleomycin model of pulmonary fibrosis and mice overexpressing Fra-2. The latter spontaneously develop pulmonary fibrosis in older age. LRP1 gene inactivation in AETII cells markedly aggravated bleomycin-induced pulmonary fibrosis as evident by increased mortality, reduced lung compliance, exaggerated deposition of ECM proteins, and aberrant activation of the TGF-β signaling pathway. Surprisingly, loss of LRP1 increased lung collagen I expression even without bleomycin treatment. These findings indicate that LRP1 is critical for maintenance of lung tissue homeostasis and proper regeneration of lung tissue after injury. Thus, reconstitution of LRP1 expression offers a potential therapeutic option for the treatment of pulmonary fibrosis.