A novel role for PRL in regulating epithelial cell density by inducing apoptosis at confluence.

Autor:	Lohani S; Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan., Funato Y; Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan., Akieda Y; Department of Homeostatic Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan., Mizutani K; Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0047, Japan., Takai Y; Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0047, Japan., Ishitani T; Department of Homeostatic Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.; Center for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Osaka 565-0871, Japan., Miki H; Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.; Center for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Osaka 565-0871, Japan.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2022 Jan 15; Vol. 135 (2). Date of Electronic Publication: 2022 Jan 26.
DOI:	10.1242/jcs.258550
Abstrakt:	Maintaining proper epithelial cell density is essential for the survival of multicellular organisms. Although regulation of cell density through apoptosis is well known, its mechanistic details remain elusive. Here, we report the involvement of membrane-anchored phosphatase of regenerating liver (PRL), originally known for its role in cancer malignancy, in this process. In epithelial Madin-Darby canine kidney cells, upon confluence, doxycycline-induced expression of PRL upregulated apoptosis, reducing cell density. This could be circumvented by artificially reducing cell density via stretching the cell-seeded silicon chamber. Moreover, small interfering RNA-mediated knockdown of endogenous PRL blocked apoptosis, leading to greater cell density. Mechanistically, PRL promoted apoptosis by upregulating the translation of E-cadherin and activating the TGF-β pathway. Morpholino-mediated inhibition of PRL expression in zebrafish embryos caused developmental defects, with reduced apoptosis and increased epithelial cell density during convergent extension. Overall, this study revealed a novel role for PRL in regulating density-dependent apoptosis in vertebrate epithelia. This article has an associated First Person interview with the first author of the paper. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2022. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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