Journalartikel
Autorenliste: Knoell, Jessica; Chillappagari, Shashi; Knudsen, Lars; Korfei, Martina; Dartsch, Ruth; Jonigk, Danny; Kuehnel, Mark P.; Hoetzenecker, Konrad; Guenther, Andreas; Mahavadi, Poornima
Jahr der Veröffentlichung: 2022
Zeitschrift: Cellular and Molecular Life Sciences
Bandnummer: 79
Heftnummer: 3
ISSN: 1420-682X
eISSN: 1420-9071
Open Access Status: Hybrid
DOI Link: https://doi.org/10.1007/s00018-022-04189-2
Verlag: Springer
Abstract:
Endoplasmic reticulum (ER) and mitochondria (mito) play a vital role in alveolar type II cell (AEC2) homeostasis and are both stressed in patients with idiopathic pulmonary fibrosis (IPF). Up to now, no data are available with regard to ER-mito cross talk and tethering under conditions of IPF. We here demonstrate that ER-mitochondrial tethering is reduced upon experimental ER stress in vitro and in the IPF AECII ex vivo, and this is-at least in part-due to decreased phosphofurin acidic cluster sorting protein 2 (PACS-2, also called PACS2) protein levels. PACS2 levels are influenced by its interaction with the transient receptor potential cation channel subfamily V member 1 (TRPV1) and can be experimentally modified by the TRPV1-modulating drug capsaicin (CPS). Employing alveolar epithelial cells with overexpression of the terminal ER stress signaling factor Chop or the IPF-associated surfactant protein C mutation (SPC Delta exon4) in vitro, we observed a restoration of PACS2 levels upon treatment with CPS. Similarly, treatment of precision cut lung slices from IPF patients with CPS ex vivo forwarded similar effects. Importantly, in all models such kind of intervention also greatly reduced the extent of alveolar epithelial apoptosis. We therefore conclude that therapeutic targeting of the PACS2-TRPV1 axis represents an interesting novel, epithelial-protective approach in IPF.
Zitierstile
Harvard-Zitierstil: Knoell, J., Chillappagari, S., Knudsen, L., Korfei, M., Dartsch, R., Jonigk, D., et al. (2022) PACS2-TRPV1 axis is required for ER-mitochondrial tethering during ER stress and lung fibrosis, Cellular and Molecular Life Sciences, 79(3), Article 151. https://doi.org/10.1007/s00018-022-04189-2
APA-Zitierstil: Knoell, J., Chillappagari, S., Knudsen, L., Korfei, M., Dartsch, R., Jonigk, D., Kuehnel, M., Hoetzenecker, K., Guenther, A., & Mahavadi, P. (2022). PACS2-TRPV1 axis is required for ER-mitochondrial tethering during ER stress and lung fibrosis. Cellular and Molecular Life Sciences. 79(3), Article 151. https://doi.org/10.1007/s00018-022-04189-2
Schlagwörter
CAPSAICIN; CHOP; Idiopathic pulmonary fibrosis; Mitochondrial associated membranes; PACS PROTEINS; TRPV1
