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Intestinal epithelial integrity is commonly disrupted in patients with critical disorders, but the exact underlying mechanisms are unclear. Long noncoding RNAs transcribed from ultraconserved regions (T-UCRs) control different cell functions and are involved in pathologies. Here, we investigated the role of T-UCRs in intestinal epithelial homeostasis and identified T-UCR uc.230 as a major regulator of epithelial renewal, apoptosis, and barrier function. Compared with controls, intestinal mucosal tissues from patients with ulcerative colitis and from mice with colitis or fasted for 48 hours had increased levels of uc.230. Silencing uc.230 inhibited the growth of intestinal epithelial cells (IECs) and organoids and caused epithelial barrier dysfunction. Silencing uc.230 also increased IEC vulnerability to apoptosis, whereas increasing uc.230 levels protected IECs against cell death. In mice with colitis, reduced uc.230 levels enhanced mucosal inflammatory injury and delayed recovery. Mechanistic studies revealed that uc.230 increased CUG-binding protein 1 (CUGBP1) by acting as a natural decoy RNA for miR-503, which interacts with Cugbp1 mRNA and represses its translation. These findings indicate that uc.230 sustains intestinal mucosal homeostasis by promoting epithelial renewal and barrier function and that it protects IECs against apoptosis by serving as a natural sponge for miR-503, thereby preserving CUGBP1 expression.
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http://dx.doi.org/10.1172/jci.insight.156612 | DOI Listing |
Arch Toxicol
December 2024
Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016, Lisbon, Portugal.
Emerging cellulose nanomaterials (CNMs) may have commercial impacts in multiple sectors, being their application particularly explored in the food sector. Thus, their potential adverse effects in the gastrointestinal tract should be evaluated before marketing. This work aimed to assess the safety of two CNMs (CNF-TEMPO and CMF-ENZ) through the investigation of their cytotoxicity, genotoxicity (comet and micronucleus assays), and capacity to induce reactive oxygen species in human intestinal cells, and their mutagenic effect using the Hprt gene mutation assay.
View Article and Find Full Text PDFChin Med
December 2024
Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, China.
Background: Liuweizhiji Gegen-Sangshen oral liquid (LGS), as a Chinese medicinal preparation, is developed from a Traditional Chinese medicinal formula consisting of six Chinese medicinal herbs, including Puerariae lobatae radix, Hoveniae semen, Imperatae rhizoma, Crataegi fructus, Mori fructus and Canarli fructus, and has been extensively utilized in the prevention and treatment of alcoholic liver disease (ALD) clinically. Previous study has demonstrated that LGS dose-dependently mitigated ALD in rat models. However, whether and how the main characteristic constituents of LGS (the flavonoid and polysaccharide fractions, LGSF and LGSP) contribute to the anti-ALD effect remains unclear.
View Article and Find Full Text PDFBMC Biol
December 2024
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Background: The mucus layer provides the first defense that keeps the epithelium free from microorganisms. However, the effect of the small intestinal mucus layer on pathogen invasion is still poorly understood, especially for swine enteric coronavirus. To better understand virus‒mucus layer‒intestinal epithelium interactions, here, we developed a porcine intestinal organoid mucus‒monolayer model under air‒liquid interface (ALI) conditions.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
December 2024
Health and Biosecurity, CSIRO,, Sydney, New South Wales Australia.
The intestinal microenvironment represents a complex and dynamic ecosystem, comprising a diverse range of epithelial and non-epithelial cells, a protective mucus layer, and a diverse community of gut microbiota. Understanding the intricate interplay between these components is essential for uncovering the mechanisms underlying intestinal health and disease. The development of intestinal organoids, 3D mini-intestines that closely mimic the architecture, cellular diversity, and functionality of the intestine, offers a powerful platform for investigating different aspects of intestinal physiology and pathology.
View Article and Find Full Text PDFProbiotics Antimicrob Proteins
December 2024
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, 210095, China.
This study aimed to investigate the effect of a multi-strain probiotic (Bifidobacterium B8101, Lactobacillus L8603, Saccharomyces bayanus S9308, Enterococcus SF9301), betaine, and their combination on intestinal epithelial development and growth performance in broilers. A total of 2800 one-day-old Ross 308 chickens were randomly divided into four groups: control (Ctrl) fed with a basal diet, multi-strain probiotic (Pb) group fed with basal diet + 100 mg/day/bird probiotic (1-14 d), betaine (Bet) fed with basal diet + 0.1% betaine (1-35 d), and a combination (Pb&Bet) fed with both probiotics and betaine.
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