• Title/Summary/Keyword: Luminal Environment

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MicroRNA-orchestrated pathophysiologic control in gut homeostasis and inflammation

  • Lee, Juneyoung;Park, Eun Jeong;Kiyono, Hiroshi
    • BMB Reports
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    • v.49 no.5
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    • pp.263-269
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    • 2016
  • The intestine represents the largest and most elaborate immune system organ, in which dynamic and reciprocal interplay among numerous immune and epithelial cells, commensal microbiota, and external antigens contributes to establishing both homeostatic and pathologic conditions. The mechanisms that sustain gut homeostasis are pivotal in maintaining gut health in the harsh environment of the gut lumen. Intestinal epithelial cells are critical players in creating the mucosal platform for interplay between host immune cells and luminal stress inducers. Thus, knowledge of the epithelial interface between immune cells and the luminal environment is a prerequisite for a better understanding of gut homeostasis and pathophysiologies such as inflammation. In this review, we explore the importance of the epithelium in limiting or promoting gut inflammation (e.g., inflammatory bowel disease). We also introduce recent findings on how small RNAs such as microRNAs orchestrate pathophysiologic gene regulation.

Chronic Low-Dose Nonylphenol or Di-(2-ethylhexyl) Phthalate has a Different Estrogen-like Response in Mouse Uterus

  • Kim, Juhye;Cha, Sunyeong;Lee, Min Young;Hwang, Yeon Jeong;Yang, Eunhyeok;Ryou, Chongsuk;Jung, Hyo-Il;Cheon, Yong-Pil
    • Development and Reproduction
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    • v.22 no.4
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    • pp.379-391
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    • 2018
  • Through the development of organic synthetic skill, chemicals that mimic signaling mediators such as steroid hormones have been exposed to the environment. Recently, it has become apparent that this circumstance should be further studied in the field of physiology. Estrogenic action of chronic low-dose nonylphenol (NP) and di-(2-ethylhexyl) phthalate (DEHP) in mouse uterus was assessed in this study. Ten to twelve-week-old female mice (CD-1) were fed drinking water containing NP (50 or $500{\mu}g/L$) or DEHP (133 or $1,330{\mu}g/L$) for 10 weeks. Uterine diameter, the thickness of myometrium and endometrium, and the height of luminal epithelial cells were measured and the number of glands were counted. The expression levels of the known $17{\beta}$-estradiol ($E_2$)-regulated genes were evaluated with real-time RT-PCR methodology. The ration of uterine weight to body weight increased in $133{\mu}g/L$ DEHP. Endometrial and myometrial thickness increased in 133 and $1,330{\mu}g/L$ DEHP treated groups, and in 50, $500{\mu}g/L$ NP and $133{\mu}g/L$ DEHP, respectively. The height of luminal epithelial cell decreased in NP groups. The numbers of luminal epithelial gland were decreased in NP groups but increased in $50{\mu}g/L$ DEHP group. The histological characters of glands were not different between groups. The mRNA expression profiles of the known $17{\beta}$-estradiol ($E_2$) downstream genes, Esr1, Esr2, Pgr, Lox, and Muc1, were also different between NP and DEHP groups. The expression levels dramatically increased in some genes by the NP or DEHP. Based on these results, it is suggested that the chronic low-dose NP or DEHP works as estrogen-like messengers in uterus with their own specific gene expression-regulation patterns.

Near Infrared Spectroscopy for Measuring Purine Derivatives in Urine and Estimation of Microbial Protein Synthesis in the Rumen for Sheep

  • Atanassova, Stefka;Iancheva, Nana;Tsenkova, Roumiana
    • Proceedings of the Korean Society of Near Infrared Spectroscopy Conference
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    • 2001.06a
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    • pp.1273-1273
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    • 2001
  • The efficiency of the luminal fermentation process influences overall efficiency of luminal production, animal health and reproduction. Ruminant production systems have a significant impact on the global environment, as well. Animal wastes contribute to pollution of the environment as ammonia volatilized to the air and nitrate leached to ground water. Microbial protein synthesis in the rumen satisfies a large proportion of the protein requirements of animals. Quantifying the microbial synthesis is possible by using markers for lumen bacteria and protozoa such as nucleic acids, purine bases, some specific amino acids, or by isotopic $^{15}N,^{32}P,\;and\;^{35}S$ labelled feeds. All those methods require cannulated animals, they are time-consuming and some methods are very expensive as well. Many attempts have been made to find an alternative method for indirect measurement of microbial synthesis in intact animals. The present investigations aimed to assess possibilities of NIRS for prediction of purine nitrogen excretion and ruminal microbial nitrogen synthesis by NIR spectra of urine. Urine samples were collected from 12 growing sheep,6 of them male, and 6- female. The sheep were included in feeding experiment. The ration consisted of sorghum silage and protein supplements -70:30 on dry matter basis. The protein supplements were chosen to differ in protein degradability. The urine samples were collected daily in a vessel containing $60m{\ell}$ 10% sulphuric acid to reduce pH below 3 and diluted with tap water to 4 liters. Samples were stored in plastic bottles and frozen at $-20^{\circ}C$ until chemical and NIRS analysis. The urine samples were analyzed for purine derivates - allantoin, uric acid, xantine and hypoxantine content. Microbial nitrogen synthesis in the lumen was calculated according to Chen and Gomes, 1995. Transmittance urine spectra with sample thickness 1mm were obtained by NIR System 6500 spectrophotometer in the spectral range 1100-2500nm. The calibration was performed using ISI software and PLS regression, respectively. The following statistical results of NIRS calibration for prediction of purine derivatives and microbial protein synthesis were obtained.(Table Omitted). The result of estimation of purine nitrogen excretion and microbial protein synthesis by NIR spectra of urine showed accuracy, adequate for rapid evaluation of microbial protein synthesis for a large number of animals and different diets. The results indicate that the advantages of the NIRS technology can be extended into animal physiological studies. The fast and low cost NIRS analyses could be used with no significant loss of accuracy when microbial protein synthesis in the lumen and the microbial protein flow in the duodenum are to be assessed by NIRS.

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The expression and localization of V-ATPase and cytokeratin 5 during postnatal development of the pig epididymis

  • Park, Yun-Jae;Kim, Ji-Hyuk;Kim, Hack-Youn;Park, Hee-Bok;Choe, Juhui;Kim, Gye-Woong;Baek, Sun-Young;Chung, Hak-Jae;Park, Yoo-Jin;Kim, Bongki
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.7
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    • pp.1077-1086
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    • 2020
  • Objective: We examined the localization and expression of H+ pumping vacuolar ATPase (V-ATPase) and cytokeratin 5 (KRT5) in the epididymis of pigs, expressed in clear and basal cells, respectively, during postnatal development. Methods: Epididymides were obtained from pigs at 1, 7, 21, 60, 120, and 180 days of age; we observed the localization and expression patterns of V-ATPase and KRT5 in the different regions of these organs, namely, the caput, corpus, and cauda. The differentiation of epididymal epithelial cells was determined by immunofluorescence labeling using cell-type-specific markers and observed using confocal microscopy. Results: At postnatal day 5 (PND5), the localization of clear cells commenced migration from the cauda toward the caput. Although at PND120, goblet-shaped clear cells were detected along the entire length of the epididymis, those labeled for V-ATPase had disappeared from the corpus to cauda and were maintained only in the caput epididymis in adult pigs. In contrast, whereas basal cells labeled for KRT5 were only present in the vas deferens at birth, they were detected in all regions of the epididymis at PND60. These cells were localized at the base of the epithelium; however, no basal cells characterized by luminally extending cell projections were observed in any of the adult epididymides examined. Conclusion: The differentiation of clear and basal cells progressively initiates in a retrograde manner from the cauda to the caput epididymis. The cell-type-specific distribution and localization of the epithelial cells play important roles in establishing a unique luminal environment for sperm maturation and storage in the pig epididymis.

Changes of Mouse Gut Microbiota Diversity and Composition by Modulating Dietary Protein and Carbohydrate Contents: A Pilot Study

  • Kim, Eunjung;Kim, Dan-Bi;Park, Jae-Yong
    • Preventive Nutrition and Food Science
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    • v.21 no.1
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    • pp.57-61
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    • 2016
  • Dietary proteins influence colorectal cancer (CRC) risk, depending on their quantity and quality. Here, using pyrosequencing, we compared the fecal microbiota composition in Balb/c mice fed either a normal protein/carbohydrate diet (ND, 20% casein and 68% carbohydrate) or a high-protein/low-carbohydrate diet (HPLCD, 30% casein and 57% carbohydrate). The results showed that HPLCD feeding for 2 weeks reduced the diversity and altered the composition of the microbiota compared with the ND mice, which included a decrease in the proportion of the family Lachnospiraceae and Ruminococcaceae and increases in the proportions of the genus Bacteroides and Parabacteroides, especially the species EF09600_s and EF604598_s. Similar changes were reported in patients with inflammatory bowel disease, and in mouse models of CRC and colitis, respectively. This suggests that HPLCD may lead to a deleterious luminal environment and may have adverse effects on the intestinal health of individuals consuming such a diet.

Microbiome-Linked Crosstalk in the Gastrointestinal Exposome towards Host Health and Disease

  • Moon, Yuseok
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.19 no.4
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    • pp.221-228
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    • 2016
  • The gastrointestinal exposome represents the integration of all xenobiotic components and host-derived endogenous components affecting the host health, disease progression and ultimately clinical outcomes during the lifespan. The human gut microbiome as a dynamic exposome of commensalism continuously interacts with other exogenous exposome as well as host sentineling components including the immune and neuroendocrine circuit. The composition and diversity of the microbiome are established on the basis of the luminal environment (physical, chemical and biological exposome) and host surveillance at each part of the gastrointestinal lining. Whereas the chemical exposome derived from nutrients and other xenobiotics can influence the dynamics of microbiome community (the stability, diversity, or resilience), the microbiomes reciprocally alter the bioavailability and activities of the chemical exposome in the mucosa. In particular, xenobiotic metabolites by the gut microbial enzymes can be either beneficial or detrimental to the host health although xenobiotics can alter the composition and diversity of the gut microbiome. The integration of the mucosal crosstalk in the exposome determines the fate of microbiome community and host response to the etiologic factors of disease. Therefore, the network between microbiome and other mucosal exposome would provide new insights into the clinical intervention against the mucosal or systemic disorders via regulation of the gut-associated immunological, metabolic, or neuroendocrine system.

Expression of the ATP-gated $P2X_7$ Receptor on M Cells and Its Modulating Role in the Mucosal Immune Environment

  • Kim, Sae-Hae;Lee, Ha-Yan;Jang, Yong-Suk
    • IMMUNE NETWORK
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    • v.15 no.1
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    • pp.44-49
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    • 2015
  • Interactions between microbes and epithelial cells in the gastrointestinal tract are closely associated with regulation of intestinal mucosal immune responses. Recent studies have highlighted the modulation of mucosal immunity by microbe-derived molecules such as ATP and short-chain fatty acids. In this study, we undertook to characterize the expression of the ATP-gated $P2X_7$ receptor ($P2X_7R$) on M cells and its role in gastrointestinal mucosal immune regulation because it was poorly characterized in Peyer's patches, although purinergic signaling via $P2X_7R$ and luminal ATP have been considered to play an important role in the gastrointestinal tract. Here, we present the first report on the expression of $P2X_7R$ on M cells and characterize the role of $P2X_7R$ in immune enhancement by ATP or LL-37.

Intestinal Alkaline Phosphatase: Potential Roles in Promoting Gut Health in Weanling Piglets and Its Modulation by Feed Additives - A Review

  • Melo, A.D.B.;Silveira, H.;Luciano, F.B.;Andrade, C.;Costa, L.B.;Rostagno, M.H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.1
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    • pp.16-22
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    • 2016
  • The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influence the intestinal environment. Intestinal alkaline phosphatase (IAP) is an important apical brush border enzyme that is influenced by these factors. IAP dephosphorylates bacterial lipopolysaccharides (LPS), unmethylated cytosine-guanosine dinucleotides, and flagellin, reducing bacterial toxicity and consequently regulating toll-like receptors (TLRs) activation and inflammation. It also desphosphorylates extracellular nucleotides such as uridine diphosphate and adenosine triphosphate, consequently reducing inflammation, modulating, and preserving the homeostasis of the intestinal microbiota. The apical localization of IAP on the epithelial surface reveals its role on LPS (from luminal bacteria) detoxification. As the expression of IAP is reported to be downregulated in piglets at weaning, LPS from commensal and pathogenic gram-negative bacteria could increase inflammatory processes by TLR-4 activation, increasing diarrhea events during this phase. Although some studies had reported potential IAP roles to promote gut health, investigations about exogenous IAP effects or feed additives modulating IAP expression and activity yet are necessary. However, we discussed in this paper that the critical assessment reported can suggest that exogenous IAP or feed additives that could increase its expression could show beneficial effects to reduce diarrhea events during the post weaning phase. Therefore, the main goals of this review are to discuss IAP's role in intestinal inflammatory processes and present feed additives used as growth promoters that may modulate IAP expression and activity to promote gut health in piglets.

The Expression and Localization of ZO-1, Claudin 1, and Claudin 4 in the Pig Epididymis (돼지 정소상체에서 ZO-1, Claudin 1 및 Claudin 4의 발현 양상)

  • Park, Yun-Jae;Kim, Bongki
    • Journal of Animal Reproduction and Biotechnology
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    • v.34 no.3
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    • pp.190-196
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    • 2019
  • Tight junctions are constituents of the blood-epididymis barrier that play roles in regulating the unidirectional transcellular transport of ions, water, and solutes to maintain optimal conditions for sperm maturation and storage. Claudin 1 (Cldn1) and 4 (Cldn4) are known as tight junction proteins and are expressed in the basolateral membranes as well as tight junctions in the epididymis of rodents. Here, we examined the expression and localization of Cldn1 and 4 to determine the function of these proteins in the pig epididymis. Cldn1 was highly expressed in the basolateral membrane of epithelial cells in the caput and corpus regions of the epididymis. In the cauda region, however, Cldn1 labeling was significantly decreased in the basolateral membrane of epithelial cells. In contrast, labeling indicated that Cldn4 was expressed in the basolateral membrane in the cauda region of the epididymis and was present at punctate reactive sites in the caput and corpus regions. However, in no region of the epididymis did we detect colocalization of Cldn1 and 4 with labeled ZO-1, the distribution of which is restricted to the tight junctions. Our results indicate that Cldn1 and 4 were region-specifically expressed in the pig epididymis but not present in the tight junctions of epididymal epithelium. In addition, reciprocal regulation in specific regions of the epididymis between Cldn1 and 4 may play an important role in generating an optimal luminal environment for sperm maturation and storage in the pig epididymis.

Loss of Primary Cilia Results in the Development of Cancer in the Murine Thyroid Gland

  • Lee, Junguee;Yi, Shinae;Chang, Joon Young;Kim, Jung Tae;Sul, Hae Joung;Park, Ki Cheol;Zhu, Xuguang;Cheng, Sheue-yann;Kero, Jukka;Kim, Joon;Shong, Minho
    • Molecules and Cells
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    • v.42 no.2
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    • pp.113-122
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    • 2019
  • Communications at the interface between the apical membrane of follicular cells and the follicular lumen are critical for the homeostasis of thyroid gland. Primary cilia at the apical membrane of thyroid follicular cells may sense follicular luminal environment and regulate follicular homeostasis, although their role in vivo remains to be determined. Here, mice devoid of primary cilia were generated by thyroid follicular epithelial cell-specific deletion of the gene encoding intraflagellar transport protein 88 (Ift88). Thyroid follicular cellspecific Ift88-deficient mice showed normal folliculogenesis and hormonogenesis; however, those older than 7 weeks showed irregularly dilated and destroyed follicles in the thyroid gland. With increasing age, follicular cells with malignant properties showing the characteristic nuclear features of human thyroid carcinomas formed papillary and solid proliferative nodules from degenerated thyroid follicles. Furthermore, malignant tumor cells manifested as tumor emboli in thyroid vessels. These findings suggest that loss-of-function of Ift88/primary cilia results in malignant transformation from degenerated thyroid follicles.