Gelsenicine disrupted the intestinal barrier of Caenorhabditis elegans
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE264529 | GEO | 2026/04/21
REPOSITORIES: GEO
Similar Datasets
Project description:The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins TRX-2 and TRX-3 do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, SKN-1 transcriptional activity remains largely unaffected. Interestingly, RNA-Seq revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport and localization being most prevalent. However, one prominent lipase-related gene, lips-6, is highly up regulated upon loss of trx-1 in a skn-1-dependent manner. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism. Four samples were analyzed: Two nematode strains were analyzed, each under non-stressed and stressed (10mM NaAs) conditions
2016-04-01 | E-GEOD-77976 | biostudies-arrayexpress
Project description:Aging has been associated with a progressive decline of proteostasis, but how this process affects proteome composition remains largely unexplored. Here, we profiled more than 5,000 proteins along the lifespan of the nematode C. elegans. We find that one-third of proteins change in abundance at least 2-fold during aging, resulting in a severe proteome imbalance. These changes are reduced in the long-lived daf-2mutant but are enhanced in the short-lived daf-16 mutant. While ribosomal proteins decline and lose normal stoichiometry, proteasome complexes increase. Proteome imbalance is accompanied by widespread protein aggregation, with abundant proteins that exceed solubility contributing most to aggregate load. Notably, the properties by which proteins are selected for aggregation differ in the daf-2mutant, and an increased formation of aggregates associated with small heat-shock proteins is observed. We suggest that sequestering proteins into chaperone-enriched aggregates is a protective strategy to slow proteostasis decline during nematode aging.
2015-05-11 | PXD001364 | Pride
Project description:In the presence of stressful environments, the SKN-1 cytoprotective transcription factor is activated to induce the expression of gene targets that can restore homeostasis. However, constitutive activation of SKN-1 results in diminished health and a reduction of lifespan. Here we demonstrate the necessity to regulate the activity of SKN-1 for maintaining the longevity promoting responses associated with impaired daf-2/insulin receptor signaling, the eat-2 model of caloric restriction, and glp-1-dependent loss of germ cell proliferation. A hallmark of animals with constitutive SKN-1 activation is the age-dependent loss of somatic lipids and this phenotype is linked to the general reduction in survival in animals harboring the skn-1gf allele, but surprisingly, daf-2lf; skn-1gf double mutant animals do not redistribute somatic lipids which suggests the insulin signaling pathway functions downstream of SKN-1 in the maintenance of lipid distribution. As expected, eat-2lf; skn-1gf double mutant animals, which independently activate SKN-1, continue to display somatic lipid depletion in older ages with and without the skn-1gf activating mutation but animals lacking a proliferating germline do not redistribute somatic lipids, which supports a genetic model where SKN-1 activity is an important regulator of lipid mobilization in response to food availability to fuel the developing germline by engaging the daf-2/insulin receptor pathway.
2024-07-01 | GSE270810 | GEO
Project description:The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins TRX-2 and TRX-3 do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, SKN-1 transcriptional activity remains largely unaffected. Interestingly, RNA-Seq revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport and localization being most prevalent. However, one prominent lipase-related gene, lips-6, is highly up regulated upon loss of trx-1 in a skn-1-dependent manner. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism.
2016-04-01 | GSE77976 | GEO
Project description:Gelsenicine disrupted the intestinal barrier of Caenorhabditis elegans
| PRJNA1103087 | ENA
Project description:We tested the role of ErbB3 in small intestinal permeability. Loss of ErbB3 in the intestinal epithelium results in increased intestinal permeability and reduced expression of Pmp22. Permeability induced by LPS can be reduced by administration of the ErbB3 ligand Nrg1.
2025-12-01 | GSE308942 | GEO
Project description:Intestinal barrier dysfunction is a hallmark of gastrointestinal disorders, including inflammatory bowel diseases (IBD). In IBD, the disruption of the gut barrier causes liquid loss and persistent immune response. Understanding the cellular events underlying epithelial barrier disruption during chronic inflammation is essential for targeting increased intestinal permeability. Filamentous actin (F-actin) destabilization accompanied by metabolic dysfunction has been previously reported in the Muc2 knockout colitis model; however, the mechanistic contribution of these defects to chronic intestinal barrier loss remains unclear. Here, we identify impaired cytoskeleton dynamics as a critical driver of intestinal barrier dysfunction in chronic colitis. An imbalance between polymeric and monomeric actin disrupts the epithelial barrier in both 3D organoid system and in vivo. Actin and associated factors were identified as primary interactors of claudin-3, and this interaction was reduced under chronic inflammatory conditions in vivo. Further analysis revealed ceramide metabolism as a potential metabolic regulator of actin dynamics and barrier integrity during chronic inflammation. Consistently, intestinal samples from IBD patients showed concurrent disruption of tight and adherens junctions and reduced F-actin levels. Together, these findings reveal F-actin dynamics as one of the key mechanisms of barrier dysfunction in IBD and highlight ceramide metabolism as a potential therapeutic target in IBD.
2026-04-01 | PXD076239 | Pride
Project description:Probiotics have been suggested to ameliorate the function of the intestinal epithelial barrier and so have several mediators and receptors of the expanded endocannabinoid system, the endocannabinoidome (eCBome). Here we cocultured three live strains of Lactiplantibacillus plantarum with intestinal epithelial organoids to study their effects on the gut barrier function and the possible involvement of the eCBome in this effect. All three L.plantarum strains variously reduced the trans-epithelial permeability of intestinal organoids and promoted increased mRNA expression of several tight junction proteins and intestinal barrier proteins. Concomitantly, the three strains upregulated the expression of genes encoding biosynthetic enzymes (i.e., NapePLD, Abdh4, Gde1, Daglb) and receptors (i.e., Cnr1, Cnr2, Gpr55, and Ppara), while concurrently downregulating the expression of two essential catabolic enzymes (i.e. Faah and Naaa), involved in the signaling of several eCBome mediators known for their role in regulating the intestinal epithelial barrier. Selective inhibitors of eCBome mediator degrading enzymes FAAH and MAGL, i.e., URB597 and JZL184, increased N-acyl-ethanolamine (NAE) and 2-monoacylglycerol (2-MAG) levels, respectively, enhanced the expression of intestinal epithelial barrier genes and reduced the trans-epithelial permeability of organoids, as for L. plantarum strains. Interestingly, inflammation-induced trans-epithelial permeability in organoids was also reversed by both FAAH and MAGL inhibitors. We surmise that elevated endogenous levels of either NAEs or 2-MAGs promote improvement in small intestine trans-epithelial permeability and that L. plantarum strains may exploit this mechanism to promote these beneficial effects.
2025-01-31 | GSE263720 | GEO
Project description:Intestinal barrier dysfunction is a hallmark of gastrointestinal disorders, including inflammatory bowel diseases (IBD). In IBD, the disruption of the gut barrier causes fluid loss and persistent immune response. Understanding the cellular events underlying epithelial barrier disruption during chronic inflammation is essential for targeting increased intestinal permeability. Filamentous actin (F-actin) destabilization accompanied by metabolic dysfunction has previously been reported in the Muc2 knockout colitis model; however, the mechanistic contribution of these defects to chronic intestinal barrier loss remains unclear. Here, we identify impaired cytoskeleton dynamics as a critical driver of intestinal barrier dysfunction in chronic colitis. An imbalance between polymeric and monomeric actin disrupts the epithelial barrier in both a 3D organoid system and in vivo. Actin and associated factors were identified as primary interactors of claudin-3, and this interaction was reduced under chronic inflammatory conditions in vivo. Further analysis revealed ceramide metabolism as a potential metabolic regulator of actin dynamics and barrier integrity during chronic inflammation. Consistently, intestinal samples from IBD patients showed concurrent disruption of tight and adherens junctions and reduced F-actin levels. Together, these findings reveal F-actin dynamics as one of the key mechanisms of barrier dysfunction in IBD and highlight ceramide metabolism as a potential therapeutic target in IBD.
2026-06-24 | GSE336404 | GEO
Project description:The role of ellagic acid (EA), a natural antioxidant, in regulating anti-aging and its underlying mechanisms remains unclear. In this study, we investigated the anti-aging effects and molecular mechanisms of EA in Caenorhabditis elegans (C. elegans). Our results demonstrate that EA extends the lifespan of C. elegans, enhances motility, reduces lipofuscin accumulation, and improves overall healthspan. Additionally, EA reduces reactive oxygen species (ROS) accumulation in C. elegans under conditions of heat and oxidative stress. The insulin/IGF-1 signaling (IIS) pathway, a key regulator of longevity and stress resistance in C. elegans, was found to mediate EA's effects. EA treatment did not extend the lifespan of mutants defective in daf-2, daf-16, hsf-1, hlh-30, and skn-1, confirming that EA’s lifespan-extending effect operates through the IIS pathway. Furthermore, EA treatment increased the expression of stress response genes downstream of the IIS pathway. Based on RNA sequencing data, we further explored the molecular mechanisms and potential regulatory roles of EA in anti-aging.
2025-05-10 | GSE295741 | GEO