Short-term transcriptomic response to plasma membrane injury.

Autor: Häger SC; Membrane Integrity, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark., Dias C; Membrane Integrity, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark., Sønder SL; Membrane Integrity, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark., Olsen AV; Computational Biology Laboratory, Center for Autophagy, Recycling and Disease, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark., da Piedade I; Computational Biology Laboratory, Center for Autophagy, Recycling and Disease, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark., Heitmann ASB; Membrane Integrity, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark., Papaleo E; Computational Biology Laboratory, Center for Autophagy, Recycling and Disease, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark.; Translational Disease Systems Biology, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark., Nylandsted J; Membrane Integrity, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark. jnl@cancer.dk.; Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, 2200, Copenhagen N, Denmark. jnl@cancer.dk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Sep 27; Vol. 11 (1), pp. 19141. Date of Electronic Publication: 2021 Sep 27.
DOI: 10.1038/s41598-021-98420-y
Abstrakt: Plasma membrane repair mechanisms are activated within seconds post-injury to promote rapid membrane resealing in eukaryotic cells and prevent cell death. However, less is known about the regeneration phase that follows and how cells respond to injury in the short-term. Here, we provide a genome-wide study into the mRNA expression profile of MCF-7 breast cancer cells exposed to injury by digitonin, a mild non-ionic detergent that permeabilizes the plasma membrane. We focused on the early transcriptional signature and found a time-dependent increase in the number of differentially expressed (> twofold, P < 0.05) genes (34, 114 and 236 genes at 20-, 40- and 60-min post-injury, respectively). Pathway analysis highlighted a robust and gradual three-part transcriptional response: (1) prompt activation of immediate-early response genes, (2) activation of specific MAPK cascades and (3) induction of inflammatory and immune pathways. Therefore, plasma membrane injury triggers a rapid and strong stress and immunogenic response. Our meta-analysis suggests that this is a conserved transcriptome response to plasma membrane injury across different cell and injury types. Taken together, our study shows that injury has profound effects on the transcriptome of wounded cells in the regeneration phase (subsequent to membrane resealing), which is likely to influence cellular status and has been previously overlooked.
(© 2021. The Author(s).)
Databáze: MEDLINE
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