| First Author | Kesireddy VS | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 11 | Pages | 12392-12408 |
| PubMed ID | 31431059 | Mgi Jnum | J:292148 |
| Mgi Id | MGI:6435566 | Doi | 10.1096/fj.201900854R |
| Citation | Kesireddy VS, et al. (2019) Susceptibility of microtubule-associated protein 1 light chain 3beta (MAP1LC3B/LC3B) knockout mice to lung injury and fibrosis. FASEB J 33(11):12392-12408 |
| abstractText | 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 3beta (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.-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 3beta (MAP1LC3B/LC3B) knockout mice to lung injury and fibrosis. |
