• Korean Journal of Veterinary Research
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• v.56 no.2
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• pp.57-66
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• 2016

The gut epithelial barrier, which is composed of the mucosal layer and the intestinal epithelium, has multiple defense mechanisms and interconnected regulatory mechanisms against enteric microbial pathogens. However, many bacterial pathogens have highly evolved infectious stratagems that manipulate mucin production, epithelial cell-cell junctions, cell death, and cell turnover to promote their replication and pathogenicity in the gut epithelial barrier. In this review, we focus on current knowledge about how bacterial pathogens regulate mucin levels to circumvent the epithelial mucus barrier and target cell-cell junctions to invade deeper tissues and increase their colonization. We also describe how bacterial pathogens manipulate various modes of epithelial cell death to facilitate bacterial dissemination and virulence effects. Finally, we discuss recent investigating how bacterial pathogens regulate epithelial cell turnover and intestinal stem cell populations to modulate intestinal epithelium homeostasis.

• Korean Journal of Veterinary Research
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• v.32 no.1
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• pp.1-6
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• 1992

The turnover time of the mucosal epithelium in the small intestine(jejunum and ilium) and large interstine(cecum), and the cells in the lamina propria of the small intestine was investigated with the radioautography in mice at various times after single injection of $^3H$-thymidine. Twenty suckling mice were sacrified at each of the following time intervals after injection ; 2 hrs, 1, 3, 5. 7, 14 and 17 days. 1. The labeled index of the epithelial cells in the crypt and the villus of the small intestine averaged 98.7% and 1.3% at 2 hrs, 982% and 1.8% at 1 day, 18.7% and 81.3% at 3 days, 6.3% and 93.7% at 5 days, respectively. The labeled index of the epithelial cells of the crypt-base, the upper-crypt and the mucosal surface in the large intestine averaged 71.8%, 28.2% and 0% at 2 hrs, 45%. 54.2% and 0% at 1 day, 17.2%, 54.5% and 28.2% at 3 days, 10.2%, 32.4% and 57.4% at 5 days, respectively. This result suggested that the turnover time of all the epithelial cells migrating from crypts to villi in the direction of the villus tips was calculated to be less than 5 days, and also the longest turnover time was calculated to be no longer than 7 day. 2. The labeled index of the total cells in the lamina propria of the small intestine averaged 6.2-7% at 2 hrs to 5 days, 4.7% at 7 days 2.6% at 17 days and this index is tend to be decreased moderately at 7 days and severely at 17 days. So this result suggested that the turnover time of the cells with the shorter cycle duration in the lamina propria of the small intestine were less than 5 days and that of the cells with the longer cycle duration more than 17 days.

• Parasites, Hosts and Diseases
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• v.52 no.3
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• pp.273-280
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• 2014

The changing patterns of goblet cell hyperplasia, intestinal epithelial cell turnover, and intestinal motility were studied in ICR and C57BL/6 mice infected with Gymnophalloides seoi (Digenea: Gymnophallidae). Whereas ICR mice retained G. seoi worms until day 7 post-infection (PI), C57BL/6 mice showed a rapid worm expulsion within day 3 PI. Immunosuppression with Depo-Medrol significantly delayed the worm expulsion in C57BL/6 mice. Goblet cell counts were increased in both strains of mice, peaking at day 1 PI in C57BL/6 mice and slowly increasing until day 7 PI in ICR mice. In C57BL/6 mice infected with G. seoi, newly proliferating intestinal epithelial cells were remarkably increased in the crypt, and the increase was the highest at day 1 PI. However, in ICR mice, newly proliferating intestinal epithelial cells increased slowly from day 1 to day 7 PI. Intestinal motility was increased in G. seoi-infected mice, and its chronological pattern was highly correlated with the worm load in both strains of mice. Meanwhile, immunosuppression of C57BL/6 mice abrogated the goblet cell proliferation, reduced the epithelial cell proliferation, and suppressed the intestinal motility. Goblet cell hyperplasia, increased intestinal epithelial cell turnover, and increased intestinal motility should be important mucosal defense mechanisms in G. seoi-infected C57BL/6 mice.

• Parasites, Hosts and Diseases
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• v.31 no.2
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• pp.83-90
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• 1993

We performed bromodeoxyuridine (BrdU) staining to observe the proliferation pattern of epithelial cells on the biliaJy mucosa in Clonorchis sinensis infection. Albino rats were infected with 100 metacercariae each and their livers were processed for histopathological observation after BrdU injection. Five to six sites in the liver of a rat were selected for paraffin section, and stained immunohistochemically to visualize BrdU incorporating cells. The flukes were mainly in the common bile duct and right or left hepatic bile ducts. The proportion of stained epithelial cells in the infected bile ducts where the worms were found on the section was 2.9-10.2% at 1 week after infection. 7.3-12.8% at 2 weeks, 7.3-13.4% at 5 weeks, and 8.4-14.8% at 15 weeks while in the non-infected ducts o to 2.7% cells were stained. The stained cells were mainly at the base of the mucosal layer. It is suggested that mucosal epithelial cells of the bile ducts infected with C. sinensis become hyperplastic mainly by direct and local stimulation of the worms.

• International Journal of Stem Cells
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• v.17 no.1
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• pp.51-58
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• 2024

With the activity of intestinal stem cells and continuous turnover, the gut epithelium is one of the most dynamic tissues in animals. Due to its simple yet conserved tissue structure and enteric cell composition as well as advanced genetic and histologic techniques, Drosophila serves as a valuable model system for investigating the regulation of intestinal stem cells. The Drosophila gut epithelium is in constant contact with indigenous microbiota and encounters externally introduced "non-self" substances, including foodborne pathogens. Therefore, in addition to its role in digestion and nutrient absorption, another essential function of the gut epithelium is to control the expansion of microbes while maintaining its structural integrity, necessitating a tissue turnover process involving intestinal stem cell activity. As a result, the microbiome and pathogens serve as important factors in regulating intestinal tissue turnover. In this manuscript, I discuss crucial discoveries revealing the interaction between gut microbes and the host's innate immune system, closely associated with the regulation of intestinal stem cell proliferation and differentiation, ultimately contributing to epithelial homeostasis.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.1
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• pp.63-69
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• 2003

Ten barrows, weaned at 28 days (7.2$\pm$0.1 kg BW), were used to evaluate the effects of feeding extruded full-fat soybeans on intestinal morphology and mucosal cell turnover time. All pigs were fed corn-based diets with half of the pigs receiving diets supplemented with 15.5% soybean meal and 3% soybean oil and the remaining pigs fed a diet in which the soybean meal and oil were replaced by 18.5% extruded full-fat soybeans. The pigs were individually placed in $80{\times}150cm$ metabolic cages and fed twice daily an amount approximately equal to their ad libitum intake for a period of 14 days. On day 14, pigs were weighed and then injected intraperitoneally with $^3$H]thymidine ($100{\mu}Ci/kg$ of BW, specific activity 20 Ci/mmol) 6 h after the morning meal. A pig from each treatment was killed 1, 4, 8, 16, or 24 h postinjection and intestinal tissues were collected. Daily gains for pigs fed the soybean diet and extruded full-fat soybean diet were 0.24 and 0.31 kg/day (p=0.05) with feed conversions of 1.58 and 1.39 (p=0.05), respectively. In comparison with pigs fed soybean meal, pigs fed moist extruded full-fat soybeans had a decreased crypt depth in their duodenum and cecum (p<0.1), while the villus height in the mid jejunum and ileum and the total height (villus height plus crypt depth) of the ileum and mid jejunum increased (p<0.05). The villus width in the duodenum and mid jejunum decreased (p<0.05). The number of crypt epithelial cells in the upper jejunum increased but decreased in the ileum, colon and cecum (p<0.05). The number of villus epithelial cells in the ileum and the upper and mid jejunum increased (p<0.05). The time for migration of epithelial cells in the crypt-villus column decreased (p<0.05) in all sites except the upper jejunum, ileum and cecum. The mucosal turnover rate for all intestinal sites except the upper jejunum, colon and cecum decreased (p<0.05). From these data, we conclude that inclusion of moist extruded full-fat soybeans in weanling pig diets can improve the intestinal morphology and slow the migration rate and turnover time of epithelial cells of the small intestine, especially in the mid jejunum compared with soybean meal.

• International Journal of Stem Cells
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• v.17 no.3
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• pp.213-223
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• 2024

Tissue-specific adult stem cells are pivotal in maintaining tissue homeostasis, especially in the rapidly renewing intestinal epithelium. At the heart of this process are leucine-rich repeat-containing G protein-coupled receptor 5-expressing crypt base columnar cells (CBCs) that differentiate into various intestinal epithelial cells. However, while these CBCs are vital for tissue turnover, they are vulnerable to cytotoxic agents. Recent advances indicate that alternative stem cell sources drive the epithelial regeneration post-injury. Techniques like lineage tracing and single-cell RNA sequencing, combined with in vitro organoid systems, highlight the remarkable cellular adaptability of the intestinal epithelium during repair. These regenerative responses are mediated by the reactivation of conserved stem cells, predominantly quiescent stem cells and revival stem cells. With focus on these cells, this review unpacks underlying mechanisms governing intestinal regeneration and explores their potential clinical applications.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.4
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• pp.485-492
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• 2011

The influence of high temperature on mammary cell turnover during the dry period is still unclear. The objective of this study was to investigate mammary cell turnover and p53 protein expression in the mammary tissue under high temperature conditions. Mammary gland biopsy samples from 8 dairy cows were obtained at 7, 25, 40, and 53 d during the dry period in summer or spring (n = 4, each season). Cell cycle, cell turnover, and p53 protein expression were analyzed by flow cytometry. During the dry period in summer, the percentage of mammary epithelial cells in the G0/G1 phase was the highest, but those in the S and G2/M phases were lower. However, the proportion of cells in the different stages of the cell cycle was not significantly different among the different biopsy time points, except in the G2/M phase. Under different temperature conditions, the cells were significantly different in their apoptotic rate and proliferation index; moreover, the tendencies of these indicators to change significantly differed. In general, the samples under high temperature conditions showed significantly lower apoptotic rates and proliferation indices. Under high temperature conditions, the apoptotic rate and proliferation index were the lowest (2.17% and 3.26%, respectively) at day 40, and the highest at day 53 (3.67% and 4.61%, respectively). However, under normal temperature conditions, the values of these indicators were the lowest (7.60% and 5.54%, respectively) at day 7, and almost the highest at day 25 (12.85% and 6.47%, respectively). Moreover, p53 protein expression was significantly higher under high temperature conditions than under normal temperature conditions, except at day 25. The level of p53 protein was the lowest (13.10%) under high temperature conditions at day 25, but was the highest (26.07%) under normal temperature conditions. Our findings suggest that high temperature delayed the G2/M phase of the cell cycle and the cell turnover rate, but remarkably increased p53 protein expression. Thus, the results indicate that high temperature extends the recovery period of mammary epithelial cells.

• Tuberculosis and Respiratory Diseases
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• v.81 no.2
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• pp.138-147
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• 2018

Background: Recent studies show that mitophagy, the autophagy-dependent turnover of mitochondria, mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure and contributes to the development of emphysema in vivo during chronic cigarette smoke (CS) exposure, although the underlying mechanisms remain unclear. Methods: In this study, we investigated the role of mitophagy in the regulation of CSE-exposed lung bronchial epithelial cell (Beas-2B) death. We also investigated the role of a phosphodiesterase 4 inhibitor, roflumilast, in CSE-induced mitophagy-dependent cell death. Results: Our results demonstrated that CSE induces mitophagy in Beas-2B cells through mitochondrial dysfunction and increased the expression levels of the mitophagy regulator protein, PTEN-induced putative kinase-1 (PINK1), and the mitochondrial fission protein, dynamin-1-like protein (DRP1). CSE-induced epithelial cell death was significantly increased in Beas-2B cells exposed to CSE but was decreased by small interfering RNA-dependent knockdown of DRP1. Treatment with roflumilast in Beas-2B cells inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting the expression of phospho-DRP1 and -PINK1. Roflumilast protected against cell death and increased cell viability, as determined by the lactate dehydrogenase release test and the MTT assay, respectively, in Beas-2B cells exposed to CSE. Conclusion: These findings suggest that roflumilast plays a protective role in CS-induced mitophagy-dependent cell death.

• Molecules and Cells
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• v.43 no.9
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• pp.774-783
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• 2020

The lung has a vital function in gas exchange between the blood and the external atmosphere. It also has a critical role in the immune defense against external pathogens and environmental factors. While the lung is classified as a relatively quiescent organ with little homeostatic turnover, it shows robust regenerative capacity in response to injury, mediated by the resident stem/progenitor cells. During regeneration, regionally distinct epithelial cell populations with specific functions are generated from several different types of stem/progenitor cells localized within four histologically distinguished regions: trachea, bronchi, bronchioles, and alveoli. WNT signaling is one of the key signaling pathways involved in regulating many types of stem/progenitor cells in various organs. In addition to its developmental role in the embryonic and fetal lung, WNT signaling is critical for lung homeostasis and regeneration. In this minireview, we summarize and discuss recent advances in the understanding of the role of WNT signaling in lung regeneration with an emphasis on stem/progenitor cells.