PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Kesireddy, V.S.* ; Chillappagari, S.* ; Ahuja, S.* ; Knudsen, L.* ; Henneke, I.* ; Graumann, J.* ; Meiners, S. ; Ochs, M.* ; Ruppert, C.* ; Korfei, M.* ; Seeger, W.* ; Mahavadi, P.*

Susceptibility of microtubule-associated protein 1 light chain 3 beta (MAP1LC3B/LC3B) knockout mice to lung injury and fibrosis.

FASEB J. 33, 12392-12408 (2019)
DOI PMC
Insufficient autophagy has been reported in idiopathic pulmonary fibrosis (IPF) lungs. Specific roles of autophagy-related proteins in lung fibrosis development remain largely unknown. Here, we investigated the role of autophagy marker protein microtubule-associated protein 1 light chain 3 beta (LC3B) in the development of lung fibrosis. LC3B(-/-) mice upon aging show smaller lamellar body profiles, increased cellularity, alveolar epithelial cell type II (AECII) apoptosis, surfactant alterations, and lysosomal and endoplasmic reticulum stress. Autophagosomal soluble N-ethylmaleimide-sensitive factor attachment protein receptor syntaxin 17 is increased in the AECII of aged LC3B(-/-) mice and patients with IPF. Proteasomal activity, however, remained unaltered in LC3B(-/- )mice. In vitro knockdown of LC3B sensitized mouse lung epithelial cells to bleomycin-induced apoptosis, but its overexpression was protective. In vivo, LC3B(-/-) mice displayed increased susceptibility to bleomycin-induced lung injury and fibrosis. We identified cathepsin A as a novel LC3B binding partner and its overexpression in vitro drives MLE12 cells to apoptosis. Additionally, cathepsin A is increased in the AECII of aged LC3B(-/-) mice and in the lungs of patients with IPF. Our study reveals that LC3B mediated autophagy plays essential roles in AECII by modulating the functions of proteins like cathepsin A and protects alveolar epithelial cells from apoptosis and subsequent lung injury and fibrosis.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
5.391
1.102
4
8
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Alveolar Epithelial Cells ; Lamellar Bodies ; Autophagy ; Aging ; Lysosome; Idiopathic Pulmonary-fibrosis; Lamellar Bodies; Cathepsin-a; Autophagy; Cell; Stress; Homeostasis; Inhibition; Secretion; Apoptosis
Language english
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 0892-6638
e-ISSN 1530-6860
Journal FASEB Journal
Quellenangaben Volume: 33, Issue: 11, Pages: 12392-12408 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Bethesda, Md.
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Lung Research
PSP Element(s) G-501600-004
DOI 10.1096/fj.201900854R
WOS ID WOS:000507461600062
Scopus ID 85074378929
PubMed ID 31431059
Erfassungsdatum 2019-11-25
[➜Report correction]