Human Wharton's jelly-derived mesenchymal stem cells alleviate Concanavalin A-induced fulminant hepatitis by repressing NF-κB signaling and glycolysis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE182182 | GEO | 2021/08/31
REPOSITORIES: GEO
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Project description:BackgroundFulminant hepatitis is a severe life-threatening clinical condition with rapid progressive loss of liver function. It is characterized by massive activation and infiltration of immune cells into the liver and disturbance of inflammatory cytokine production. Mesenchymal stem cells (MSCs) showed potent immunomodulatory properties. Transplantation of MSCs is suggested as a promising therapeutic approach for a host of inflammatory conditions.MethodsIn the current study, a well-established concanavalin A (Con A)-induced fulminant hepatitis mouse model was used to investigate the effects of transplanting human umbilical cord Wharton's jelly-derived MSCs (hWJ-MSCs) on fulminant hepatitis.ResultsWe showed that hWJ-MSCs effectively alleviate fulminant hepatitis in mouse models, primarily through inhibiting T cell immunity. RNA sequencing of liver tissues and human T cells co-cultured with hWJ-MSCs showed that NF-κB signaling and glycolysis are two main pathways mediating the protective role of hWJ-MSCs on both Con A-induced hepatitis in vivo and T cell activation in vitro.ConclusionIn summary, our data confirmed the potent therapeutic role of MSCs-derived from Wharton's jelly of human umbilical cord on Con A-induced fulminant hepatitis, and uncovered new mechanisms that glycolysis metabolic shift mediates suppression of T cell immunity by hWJ-MSCs.
| S-EPMC8427901 | biostudies-literature
Project description:Human Wharton's jelly-derived mesenchymal stem cells alleviate Concanavalin A-induced fulminant hepatitis by repressing NF-κB signaling and glycolysis
| PRJNA755269 | ENA
Project description:Eight-week-old male pathogen-free BALB/c mice were used for the induction of concanavalin A (Con A)-induced hepatitis. Animals were acclimated for at least 6-7 days to a 12-hour light/dark cycle in a humidity- and temperature-controlled, specific-pathogen-free environment in autoclaved cages. Mice were randomly assigned to two groups (4 in each group) and received Con A type IV (or saline) intravenously via the tail vein at the dose of 20 mg/kg for 2 hours. The animals were sacrificed for blood and liver collection. Blood was taken for transaminase and cytokine measurements. Livers were excised immediately after sacrifice. Part of the livers were immediately snap-frozen in liquid nitrogen and kept at -80°C for total RNA isolation and microRNA microarray analysis. miR-674-5p and other miRNAs were experimentally validated to be dysregulated by Con A in mouse livers. Liver samples from four mice treated with Con A and four mice treated with saline were used to acquire the miRNA expression profiling.
2016-06-27 | E-GEOD-76345 | biostudies-arrayexpress
Project description:Purpose: The goals of this study are to find the mechanisms of mesenchymal stem cells (MSC) ameliorating concanavalin A (Con A) induced inflammatory mice Methods: Liver tissues were harvested at 6h, 12h after Con A injected with/without MSC (n = 3 per group) for transcriptome profiling. Results: Filter the raw data obtained fromDNBSEQ-G400, and compare the filtered clean reads to the reference sequence. Quantitative analysis of known genes and new genes, differential expression analysis based on gene expression in different sample groups, GO function analysis, Pathway function analysis, cluster analysis, and protein interaction for the selected differentially expressed genes Network, transcription factor coding ability prediction and other in-depth mining analysis. Conclusions: Our study discoveres following processes were significantly affected: apoptosis, MAPK signaling pathway and cytokine-cytokine receptor interaction.
2023-07-01 | GSE178696 | GEO
Project description:Eight-week-old male pathogen-free BALB/c mice were used for the induction of concanavalin A (Con A)-induced hepatitis. Animals were acclimated for at least 6-7 days to a 12-hour light/dark cycle in a humidity- and temperature-controlled, specific-pathogen-free environment in autoclaved cages. Mice were randomly assigned to two groups (4 in each group) and received Con A type IV (or saline) intravenously via the tail vein at the dose of 20 mg/kg for 2 hours. The animals were sacrificed for blood and liver collection. Blood was taken for transaminase and cytokine measurements. Livers were excised immediately after sacrifice. Part of the livers were immediately snap-frozen in liquid nitrogen and kept at -80°C for total RNA isolation and microRNA microarray analysis. miR-674-5p and other miRNAs were experimentally validated to be dysregulated by Con A in mouse livers.
2016-06-27 | GSE76345 | GEO
Project description:Acute liver failure is a clinical syndrome of severe hepatic dysfunction. Immune cells play an important role in the failure. In recent years, the immunoregulatory function of extracellular vesicles (EVs) has been reported; therefore, it is inferred that EVs have some role in an immune mediated liver injury. In this study, we investigated the immunoregulatory function of EVs in a concanavalin A (Con A)-induced liver injury. The mouse model was prepared by a single intravenous administration of 15 mg/kg Con A, in which there was a significant increase in serum EVs number. In in vitro study, the secreted EVs number was also significantly increased in Con A-treated RAW264.7, a mouse macrophage cell line, but not Hepa1-6, a mouse hepatoma cell line. In in vitro EVs treatment study, the EVs from Con A-treated mice serum and Con A-treated RAW264.7 suppressed the inflammatory cytokines production in Con A-stimulated RAW264.7. miRNA sequencing analysis showed that mmu-miR-122-5p and mmu-miR-148a-3p were commonly increased in these EVs and the EVs-treated cells. The enriched pathways in the miRNAs predicted target genes included the inflammatory response pathways. mRNA levels of the target genes in the pathways (mitogen-activated protein kinase, Phosphoinositide 3-kinase/Akt and Rho/Rho associated coiled-coil containing protein kinase pathways) were decreased in the EVs-treated cells. In in vivo RNA interference study, knock down of liver RAB27A, an EVs secretion regulator, significantly exacerbated the Con A-induced liver injury. These data suggest that macrophage-derived EVs play an important role in a Con A-induced liver injury through the immunoregulation.
2020-03-20 | GSE147243 | GEO
Project description:Fulminant hepatic failure (FHF) is a potentially fatal liver disease that is associated with intrahepatic infiltration of inflammatory cells. As the receptor of polyunsaturated long chain fatty acids, GPR120 can regulate cell differentiation, proliferation, metabolism, and immune response. However, whether GPR120 is involved in FHF remains unknown. Using Propionibacterium acnes (P. acnes)-primed, LPS-induced FHF in mice, we found that interference with GPR120 activity using pharmacological agonist attenuated the severity of the liver injury and mortality of FHF in mice, while a lack of GPR120 exacerbated the disease. GPR120 activation potently alleviated FHF and led to decreased T helper (Th) 1 cell response and expansion of regulatory T cells (Tregs). Interestingly, GPR120 agonist didn't directly target T cells, but dramatically induced a distinct population of CD11c+MHC IIlowCD80lowCD86low regulatory DCs in the livers of FHF mice. GPR120 was found to restrict HIF-1α-dependent glycolysis. The augmented HIF-1α stabilization caused by GPR120 antagonism or deletion could be attenuated by the inhibition of ERK or by the activation of AMPK. Through the analysis of the clinical FHF, we further confirmed the activation of GPR120 was negatively associated with the severity in patients. Our findings indicated that GPR120 activation has therapeutic potential in FHF. Strategies to target GPR120 using agonists or free fatty acids (FFAs) may represent a novel approach to FHF treatment.
| S-EPMC8674251 | biostudies-literature
Project description:Human umbilical cord Wharton’s jelly stem cells (WHJSC) are gaining attention as a possible clinical source of mesenchymal stem cells for use in cell therapy and tissue engineering due to their high accessibility, expansion potential and plasticity. However, the cell viability changes that are associated to sequential cell passage of these cells are not known. In this analysis, we have identified the gene expression changes that are associated to cell passage in WHJSC. We used microarrays to detail the global programme of gene expression underlying cell passage on WHJSC.
2011-07-06 | GSE30391 | GEO
Project description:To investigate the effect of YTHDF1 on concanavalin A (ConA)-induced hepatitis , we performed RNA-seq with the total RNA extracted from the moue liver. Ythdf1-/- or wild type mice were intravenously injected with ConA (8 mg/kg) or saline for 8 hours. Then, the livers were collected, homogenized, and subjected to total RNA extraction.
2023-08-08 | GSE238229 | GEO
Project description:BACKGROUND:The last decade has seen an explosion in the interest in using biologics for regenerative medicine applications, including umbilical cord-derived Wharton's Jelly. There is insufficient literature assessing the amount of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes in these products. The present study reports the development of a novel Wharton's jelly formulation and evaluates the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes. METHODS:Human umbilical cords were obtained from consenting caesarian section donors. The Wharton's jelly was then isolated from the procured umbilical cord and formulated into an injectable form. Randomly selected samples from different batches were analyzed for sterility testing and to quantify the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles. RESULTS:All samples passed the sterility test. Growth factors including IGFBP 1, 2, 3, 4, and 6, TGF-?, and PDGF-AA were detected. Several immunomodulatory cytokines, such as RANTES, IL-6R, and IL-16, were also detected. Pro-inflammatory cytokines MCSFR, MIP-1a; anti-inflammatory cytokines TNF-RI, TNF-RII, and IL-1RA; and homeostatic cytokines TIMP-1 and TIMP-2 were observed. Cytokines associated with wound healing, ICAM-1, G-CSF, GDF-15, and regenerative properties, GH, were also expressed. High concentrations of hyaluronic acid were observed. Particles in the extracellular vesicle size range were also detected and were enclosed by the membrane, indicative of true extracellular vesicles. CONCLUSION:There are numerous growth factors, cytokines, hyaluronic acid, and extracellular vesicles present in the Wharton's jelly formulation analyzed. The amount of these factors in Wharton's jelly is higher compared with other biologics and may play a role in reducing inflammation and pain and augment healing of musculoskeletal injuries.
| S-EPMC7017504 | biostudies-literature