scholarly journals A novel role of PRL in regulating epithelial cell density by inducing apoptosis at confluence

2021 ◽  
Author(s):  
Sweksha Lohani ◽  
Yosuke Funato ◽  
Yuki Akieda ◽  
Kiyohito Mizutani ◽  
Yoshimi Takai ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Density ◽  
Mdck Cells ◽  
Zebrafish Embryos ◽  
Developmental Defect ◽  
Convergent Extension ◽  
Regenerating Liver ◽  
Phosphatase Of Regenerating Liver ◽  
Multicellular Organisms

Maintaining proper epithelial cell density is essential for the survival of multicellular organisms. While 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 MDCK cells, upon confluence, doxycycline-induced expression of PRL upregulated apoptosis, reducing the cell density. This could be circumvented by artificially reducing the cell density via stretching the cell-seeded silicon chamber. Moreover, siRNA-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 TGF-β pathway. Morpholino-mediated inhibition of PRL expression in zebrafish embryos caused developmental defect with reduced apoptosis and increased epithelial cell density during convergent extension. This study revealed a novel role of PRL in regulating density-dependent apoptosis in vertebrate epithelium.

scholarly journals The ZO-1–associated Y-box factor ZONAB regulates epithelial cell proliferation and cell density

2003 ◽  
Vol 160 (3) ◽  
pp. 423-432 ◽  
Author(s):  
Maria S. Balda ◽  
Michelle D. Garrett ◽  
Karl Matter
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Tight Junctions ◽  
Cell Density ◽  
Mdck Cells ◽  
Nuclear Accumulation ◽  
Regulation Of Transcription ◽  
Epithelial Cell Proliferation ◽  
Nucleic Acid Binding ◽  
Nucleic Acid Binding Proteins

Epithelial tight junctions regulate paracellular permeability, restrict apical/basolateral intramembrane diffusion of lipids, and have been proposed to participate in the control of epithelial cell proliferation and differentiation. Previously, we have identified ZO-1–associated nucleic acid binding proteins (ZONAB), a Y-box transcription factor whose nuclear localization and transcriptional activity is regulated by the tight junction–associated candidate tumor suppressor ZO-1. Now, we found that reduction of ZONAB expression using an antisense approach or by RNA interference strongly reduced proliferation of MDCK cells. Transfection of wild-type or ZONAB-binding fragments of ZO-1 reduced proliferation as well as nuclear ZONAB pools, indicating that promotion of proliferation by ZONAB requires its nuclear accumulation. Overexpression of ZONAB resulted in increased cell density in mature monolayers, and depletion of ZONAB or overexpression of ZO-1 reduced cell density. ZONAB was found to associate with cell division kinase (CDK) 4, and reduction of nuclear ZONAB levels resulted in reduced nuclear CDK4. Thus, our data indicate that tight junctions can regulate epithelial cell proliferation and cell density via a ZONAB/ZO-1–based pathway. Although this regulatory process may also involve regulation of transcription by ZONAB, our data suggest that one mechanism by which ZONAB and ZO-1 influence proliferation is by regulating the nuclear accumulation of CDK4.

scholarly journals An antiglycolipid antibody inhibits Madin-Darby canine kidney cell adhesion to laminin and interferes with basolateral polarization and tight junction formation.

1996 ◽  
Vol 133 (3) ◽  
pp. 695-708 ◽  
Author(s):  
G M Zinkl ◽  
A Zuk ◽  
P van der Bijl ◽  
G van Meer ◽  
K S Matlin
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cell ◽  
Mdck Cells ◽  
Collagen Type I ◽  
Cell Polarization ◽  
Type I ◽  
Adhesion Protein ◽  
Tight Junction Formation ◽  
Extracellular Matrix Molecules

Epithelial cells polarize not only in response to cell-cell contacts, but also to contacts with a substratum composed of extracellular matrix molecules. To probe the role of specific matrix constituents in epithelial cell polarization, we investigated the effects of an adhesion-blocking mAb, 12B12, on initial polarization of MDCK cells. The 12B12 antibody, raised against whole MDCK cells, blocks adhesion to laminin by 65% but has no effect on adhesion of cells to collagen type I. Taking advantage of this antibody's function-blocking activity, as well as the fact that MDCK cells secrete laminin, the role of endogenous laminin in polarization was examined by plating cells on collagen-coated substrata in the presence of the antibody. Under these conditions, cell spreading was reduced 1.5h after plating, and cells were flatter and had fewer microvilli after 24 h. Even though lateral cell membranes were closely apposed, transepithelial resistance in the presence of the antibody was significantly reduced relative to controls. When the polarization of specific apical and basolateral markers was examined both biochemically and immunocytochemically in the presence of the antibody, we observed that the apical marker polarized at normal rates while basolateral markers did not. Surprisingly, the 12B12 antibody was not directed against any known cell adhesion protein but reacted specifically with Forssman antigen, a glycosphingolipid. These results suggest that glycolipids may play a significant role in cell adhesion via laminin and in epithelial cell polarization.

Enteric glia inhibit intestinal epithelial cell proliferation partly through a TGF-β1-dependent pathway

2007 ◽  
Vol 292 (1) ◽  
pp. G231-G241 ◽  
Author(s):  
M. Neunlist ◽  
P. Aubert ◽  
S. Bonnaud ◽  
L. Van Landeghem ◽  
E. Coron ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Cell Density ◽  
Intestinal Epithelial Cell ◽  
Intestinal Barrier ◽  
Intestinal Epithelial ◽  
Epithelial Cell Proliferation ◽  
Coculture Model

Although recent studies have shown that enteric neurons control intestinal barrier function, the role of enteric glial cells (EGCs) in this control remains unknown. Therefore, our goal was to characterize the role of EGCs in the control of intestinal epithelial cell proliferation using an in vivo transgenic and an in vitro coculture model. Assessment of intestinal epithelial cell proliferation after ablation of EGCs in transgenic mice demonstrated a significant increase in crypt cell hyperplasia. Furthermore, mucosal glial network (assessed by immunohistochemical detection of S-100β) is altered in colon adenocarcinoma compared with control tissue. In an in vitro coculture model of subconfluent Caco-2 cells seeded onto Transwell filters with EGCs, Caco-2 cell density and [3H]thymidine incorporation were significantly lower than in control (Caco-2 cultured alone). Flow cytometry analysis showed that EGCs had no effect on Caco-2 cell viability. EGCs induced a significant increase in Caco-2 cell surface area without any sign of cellular hypertrophy. These effects by EGCs were also seen in various transformed or nontransformed intestinal epithelial cell lines. Furthermore, TGF-β1 mRNA was expressed, and TGF-β1 was secreted by EGCs. Exogenously added TGF-β1 reproduced partly the EGC-mediated effects on cell density and surface area. In addition, EGC effects on Caco-2 cell density were significantly reduced by a neutralizing TGF-β antibody. In conclusion, EGCs have profound antiproliferative effects on intestinal epithelial cells. Functional alterations in EGCs may therefore modify intestinal barrier functions and be involved in pathologies such as cancer or inflammatory bowel diseases.

scholarly journals A Novel Neuroprotective Role of Phosphatase of Regenerating Liver-1 against CO2 Stimulation in Drosophila

iScience ◽  
2019 ◽  
Vol 19 ◽  
pp. 291-302 ◽  
Author(s):  
Pengfei Guo ◽  
Xiao Xu ◽  
Fang Wang ◽  
Xin Yuan ◽  
Yinqi Tu ◽  
...  
Keyword(s):  
Regenerating Liver ◽  
Phosphatase Of Regenerating Liver

scholarly journals Neuroprotective role of Phosphatase of Regenerating Liver-1 against CO2 stimulation in Drosophila

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S89
Author(s):  
Yongmei Xi ◽  
Pengfei Guo ◽  
Xiao Xu ◽  
Xiaohang Yang
Keyword(s):  
Regenerating Liver ◽  
Phosphatase Of Regenerating Liver

The essential role of FKBP38 in regulating phosphatase of regenerating liver 3 (PRL-3) protein stability

2011 ◽  
Vol 406 (2) ◽  
pp. 305-309 ◽  
Author(s):  
Myung-Suk Choi ◽  
Sang-Hyun Min ◽  
Haiyoung Jung ◽  
Ju Dong Lee ◽  
Tae Ho Lee ◽  
...  
Keyword(s):  
Protein Stability ◽  
Essential Role ◽  
Regenerating Liver ◽  
Phosphatase Of Regenerating Liver

Defining the role of the phosphatase of regenerating liver enzymes in the immune system

2015 ◽  
Vol 43 (9) ◽  
pp. S66
Author(s):  
Teri Hatzihristidis ◽  
Noriko Uetani ◽  
Serge Hardy ◽  
Jacinthe Sirois ◽  
Michel L. Tremblay
Keyword(s):  
Immune System ◽  
Liver Enzymes ◽  
Regenerating Liver ◽  
Phosphatase Of Regenerating Liver

Phosphatase of regenerating liver sensitizes MET to functional activation by hepatocyte growth factor

2019 ◽  
Vol 476 (10) ◽  
pp. 1419-1431
Author(s):  
Takuya Kojima ◽  
Yosuke Funato ◽  
Hiroaki Miki
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Cellular Level ◽  
Malignant Progression ◽  
Regenerating Liver ◽  
Downstream Signaling ◽  
Phosphatase Of Regenerating Liver ◽  
Hepatocyte Growth

Abstract Phosphatase of regenerating liver (PRL) is overexpressed in metastatic cancers and actively drives their malignant progression. Many studies on cultured cancer cells have implied PRL overexpression as a stimulant for cellular signaling involved in cell proliferation. However, its role in the tightly adhered and polarized epithelial cells remains largely uncharacterized. In this study, we show that inducible expression of PRL in MDCK normal epithelial cells sensitized MET, the receptor for hepatocyte growth factor (HGF), to functional activation by HGF. We found that PRL expression amplified tyrosine phosphorylation levels of various proteins, among which MET was identified to be the most abundant. This phosphorylation occurred selectively at Y1234/1235 in the activation loop of MET, whereas phosphorylation of Y1349 in the effector-binding site, which is directly involved in downstream signaling, was almost undetectable. Consistently, PRL overexpression by itself did not cause observable alterations at the cellular level. However, when cells were stimulated with HGF, phosphorylation of Y1349 was much more strongly induced in PRL-expressing cells than in control cells. This resulted in robust cell scattering and tubulogenesis, even with low levels of HGF. Collectively, these results demonstrate a unique role of PRL in regulating MET function, which is known to be crucial for remodeling of epithelial tissues and malignant progression of cancers.

scholarly journals Role of phosphatase of regenerating liver 1 (PRL1) in spermatogenesis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yunpeng Bai ◽  
Hong-Ming Zhou ◽  
Lujuan Zhang ◽  
Yuanshu Dong ◽  
Qi Zeng ◽  
...  
Keyword(s):  
Regenerating Liver ◽  
Phosphatase Of Regenerating Liver
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