scholarly journals Wound-induced polyploidization is dependent on integrin-yki signaling

Biology Open ◽  
2020 ◽  
pp. bio.055996
Author(s):  
Rose Besen-McNally ◽  
Kayla J. Gjelsvik ◽  
Vicki P. Losick

A key step in tissue repair is to replace lost or damaged cells. This occurs via two strategies: restoring cell number through proliferation or increasing cell size through polyploidization. Studies in Drosophila and vertebrates have demonstrated that polyploid cells arise in adult tissues, at least in part, to promote tissue repair and restore tissue mass. However, the signals that cause polyploid cells to form in response to injury remain poorly understood. In the adult Drosophila epithelium, wound-induced polyploid cells are generated by both cell fusion and endoreplication, resulting in a giant polyploid syncytium. Here, we identify the integrin focal adhesion complex as an activator of wound-induced polyploidization. Both integrin and focal adhesion kinase are upregulated in the wound-induced polyploid cells and are required for Yorkie induced endoreplication and cell fusion. As a result, wound healing is perturbed when focal adhesion genes are knocked down. These findings show that conserved focal adhesion signaling is required to initiate wound-induced polyploid cell growth.

2021 ◽  
Author(s):  
Ari S Dehn ◽  
Navdeep Gogna ◽  
Patsy M Nishina ◽  
Vicki P Losick

A characteristic of normal aging and age-related diseases is the remodeling of a tissue's cellular organization through polyploid cell growth. Polyploidy arises from an increase in nuclear ploidy or the number of nuclei per cell. However, it is not known whether age-induced polyploidy is an adaption to stressors or a precursor to degeneration. Here, we find that the adult fruit fly's abdominal epithelium becomes polyploid with age through generation of large multinucleated cells that make up more than 40% of the tissue area. The syncytia arise by cell fusion, not endomitosis. Epithelial multinucleation is also a characteristic of macular degeneration, including Ctnna1tvrm5, a mouse model for pattern dystrophy. Similarly, we find that the knockdown of alpha-catenin enhances multinucleation in the fly epithelium. We further show that age-induced polyploidy can be suppressed by inhibiting cell fusion revealing a means to maintain tissue organization in older animals.


Author(s):  
R. Carriere

The external orbital gland of the albino rat exhibits both sexual dimorphism and histological age changes. In males, many cells attain a remarkable degree of polyploidy and an increase of polyploid cell number constitutes the major age change until young adulthood. The acini of young adults have a small lumen and are composed of tall serous cells. Subsequently, many acini acquire a larger lumen with an irregular outline while numerous vacuoles accumulate throughout the secretory cells. At the same time, vesicular acini with a large lumen surrounded by pale-staining low cuboidal diploid cells begin to appear and their number increases throughout old age. The fine structure of external orbital glands from both sexes has been explored and in considering acinar cells from males, emphasis was given to the form of the Golgi membranes and to nuclear infoldings of cytoplasmic constituents.


Author(s):  
Awtar Krishan ◽  
Nestor Bohonos

Cytochalasin B, a mould metabolite from Helminthosporium dermatioideum has been shown to interfere with specific cell activities such as cytoplasmic cleavage and cell movement. Cells undergoing nuclear division in the presence of cytochalasin B are unable to complete the separation of the resulting daughter cells. In time-lapse studies, the daughter cells coalesce after an initial unsuccessful attempt at separation and form large multinucleate polyploid cells. The present report describes the fine structure of the large polyploid cells induced in Earle's L-cell monolayer cultures by exposure to cytochalasin B (lγ/ml) for 92 hours.In the present material we have seen as many as 7 nuclei in these polyploid cells. Treatment with cytochalasin B for longer periods of time (6 to 7 days, with one medium change on the 3rd day) did not increase the number of nuclei beyond the 7 nuclei stage. Figure 1 shows a large polyploid cell with four nuclei. These nuclei are indistinguishable in their fine structure from those of the cells from control cultures but often show unusually large numbers of cytoplasmic invaginations and extensions of the nuclear surface (Figure 2).


2019 ◽  
Vol 19 (14) ◽  
pp. 1728-1736
Author(s):  
Xuefeng Liu ◽  
Yonggang Fan ◽  
Jing Xie ◽  
Li Zhang ◽  
Lihua Li ◽  
...  

Background:The 12-hydroxy-14-dehydroandrographolide (DP) is a predominant component of the traditional herbal medicine Andrographis paniculata (Burm. f.) Nees (Acanthaceae). Recent studies have shown that DP exhibits potent anti-cancer effects against oral and colon cancer cells.Objective:This investigation examined the potential effects of DP against osteosarcoma cell.Methods:A cell analyzer was used to measure cell viability. The cell growth and proliferation were performed by Flow cytometry and BrdU incorporation assay. The cell migration and invasion were determined by wound healing and transwell assay. The expression of EMT related proteins was examined by Western blot analysis.Results:In this study, we found that DP treatment repressed osteosarcoma (OS) cell growth in a dose-dependent manner. DP treatment significantly inhibited OS cell proliferation by arresting the cell cycle at G2/M phase. In addition, DP treatment effectively inhibited the migration and invasion abilities of OS cells through wound healing and Transwell tests. Mechanistic studies revealed that DP treatment effectively rescued the epithelialmesenchymal transition (EMT), while forced expression of SATB2 in OS cells markedly reversed the pharmacological effect of DP on EMT.Conclusion:Our data demonstrated that DP repressed OS cell growth through inhibition of proliferation and cell cycle arrest; DP also inhibited metastatic capability of OS cells through a reversal of EMT by targeting SATB2. These findings demonstrate DP’s potential as a therapeutic drug for OS treatment.


2006 ◽  
Vol 80 (3) ◽  
pp. 1181-1190 ◽  
Author(s):  
Heather B. Nelson ◽  
Hengli Tang

ABSTRACT An intimate relationship between hepatitis C virus (HCV) replication and the physiological state of the host liver cells has been reported. In particular, a highly reproducible and reversible inhibitory effect of high cell density on HCV replication was observed: high levels of HCV RNA and protein can be detected in actively growing cells but decline sharply when the replicon cells reach confluence. Arrested cell growth of confluent cells has been proposed to be responsible for the inhibitory effect. Indeed, other means of arresting cell growth have also been shown to inhibit HCV replication. Here, we report a detailed study of the effect of cell growth and confluence on HCV replication using a flow cytometry-based assay that is not biased against cytostasis and reduced cell number. Although we readily reproduced the inhibitory effect of cell confluence on HCV replication, we found no evidence of inhibition by serum starvation, which arrested cell growth as expected. In addition, we observed no inhibitory effect by agents that perturb the cell cycle. Instead, our results suggest that the reduced intracellular pools of nucleosides account for the suppression of HCV expression in confluent cells, possibly through the shutoff of the de novo nucleoside biosynthetic pathway when cells become confluent. Adding exogenous uridine and cytidine to the culture medium restored HCV replication and expression in confluent cells. These results suggest that cell growth arrest is not sufficient for HCV replicon inhibition and reveal a mechanism for HCV RNA inhibition by cell confluence.


2003 ◽  
Vol 63 (2) ◽  
pp. 722-731 ◽  
Author(s):  
Masahito Tamura ◽  
Akihiko Osajima ◽  
Shingo Nakayamada ◽  
Hirofumi Anai ◽  
Narutoshi Kabashima ◽  
...  

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