Development of microRNA signatures for acute rejection after liver transplantation using rat model
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE36798 | GEO | 2020/12/26
REPOSITORIES: GEO
Similar Datasets
Project description:Using a rat orthotopic liver transplantation (OLT) model and microarray, we compared the expression profiles of microRNAs in naïve and AR livers at day 7 after OLT obtained from the rats with short-term (<14 days, DA-LEW) or long-term (>60 days, DA-PVG) survival fate. AR-related microRNAs and pro-inflammatory cytokines were validated by using a quantitative real-time PCR. AR-related microRNA-mediated inflammatory responses were evaluated by overexpression of a target microRNA in rat primary hepatocytes. Human liver biopsies from recipients with AR or abnormal liver function were used for clinical verification. The microarray revealed that miR-301a was significantly upregulated in lethal AR livers of DA-LEW, while it was comparable to the naïve livers in DA-PVG, which spontaneously overcomes AR. OLT was carried out following the technique previously described by Kamada et al. in the following combinations: DA donor liver into PVG (DA-PVG; natural tolerance model with long-term (>60 days) and DA donor liver into LEW (DA-LEW; AR model with short-term (<14 days).
2014-12-20 | E-GEOD-64362 | biostudies-arrayexpress
Project description:Using a rat orthotopic liver transplantation (OLT) model and microarray, we compared the expression profiles of microRNAs in naïve and AR livers at day 7 after OLT obtained from the rats with short-term (<14 days, DA-LEW) or long-term (>60 days, DA-PVG) survival fate. AR-related microRNAs and pro-inflammatory cytokines were validated by using a quantitative real-time PCR. AR-related microRNA-mediated inflammatory responses were evaluated by overexpression of a target microRNA in rat primary hepatocytes. Human liver biopsies from recipients with AR or abnormal liver function were used for clinical verification. The microarray revealed that miR-301a was significantly upregulated in lethal AR livers of DA-LEW, while it was comparable to the naïve livers in DA-PVG, which spontaneously overcomes AR.
2014-12-20 | GSE64362 | GEO
Project description:Objective: Apolipoprotein E (Apo E) is a multifunctional protein, originally described in the context of lipoprotein metabolism and cardiovascular disease. More recently, anti-inflammatory functions of ApoE have been documented. ApoE was studied in the context of several inflammatory disorders, but its role in the pathogenesis of acute organ rejection is unknown. In this study, we test the hypothesis that ApoE attenuates acute renal allograft rejection. Materials and methods: The Dark Agouti (DA) to Lewis (Lew) and the Brown Norway (BN) to Lew rat strain combinations were used to investigate fatal acute rejection. In addition, Fischer 344 (F344) kidneys were transplanted to Lew rats to study reversible acute rejection. Isograft recipients and untreated Lew rats were used as controls. ApoE mRNA expression was quantified in intravascular leukocytes accumulating in the blood vessels of renal grafts and in graft tissue. Apo E protein levels were assessed in blood plasma. To test the protective potential of ApoE, recipients of BN kidneys were treated with ApoE-mimetic peptide. Results: Intravascular graft leukocytes and renal tissue obtained from animals undergoing reversible acute rejection expressed increased levels of ApoE mRNA, whereas during fatal rejection, ApoE expression remained unchanged in the BN to Lew rat strain combination or was significantly reduced when DA rats were used as donors of the kidney. On the protein level, no changes in ApoE were seen in plasma. However, we do not know if local leukocytic ApoE expression results in increased ApoE concentrations inside graft blood vessels. Peptide treatment of allograft recipients reversed fatal rejection and significantly improved animal survival. Conclusions: ApoE plays a protective role in acute organ rejection. Further studies are needed to understand the exact mechanism how ApoE reverses acute rejection. dual-color balanced dye-swap design with 4 biological replicates, hybridized on 4 arrays
2016-06-01 | E-GEOD-58156 | biostudies-arrayexpress
Project description:Objective: Apolipoprotein E (Apo E) is a multifunctional protein, originally described in the context of lipoprotein metabolism and cardiovascular disease. More recently, anti-inflammatory functions of ApoE have been documented. ApoE was studied in the context of several inflammatory disorders, but its role in the pathogenesis of acute organ rejection is unknown. In this study, we test the hypothesis that ApoE attenuates acute renal allograft rejection. Materials and methods: The Dark Agouti (DA) to Lewis (Lew) and the Brown Norway (BN) to Lew rat strain combinations were used to investigate fatal acute rejection. In addition, Fischer 344 (F344) kidneys were transplanted to Lew rats to study reversible acute rejection. Isograft recipients and untreated Lew rats were used as controls. ApoE mRNA expression was quantified in intravascular leukocytes accumulating in the blood vessels of renal grafts and in graft tissue. Apo E protein levels were assessed in blood plasma. To test the protective potential of ApoE, recipients of BN kidneys were treated with ApoE-mimetic peptide. Results: Intravascular graft leukocytes and renal tissue obtained from animals undergoing reversible acute rejection expressed increased levels of ApoE mRNA, whereas during fatal rejection, ApoE expression remained unchanged in the BN to Lew rat strain combination or was significantly reduced when DA rats were used as donors of the kidney. On the protein level, no changes in ApoE were seen in plasma. However, we do not know if local leukocytic ApoE expression results in increased ApoE concentrations inside graft blood vessels. Peptide treatment of allograft recipients reversed fatal rejection and significantly improved animal survival. Conclusions: ApoE plays a protective role in acute organ rejection. Further studies are needed to understand the exact mechanism how ApoE reverses acute rejection.
2016-06-01 | GSE58156 | GEO
Project description:To examine the influence cellular and genetics on the procainamide-induced autoimmune response in spleens we compared rats that are genetically Th2-predisposed (Brown Norway), Th1-predisposed (Lewis) or not genetically predisposed (Sprague Dawley). Rats were treated with procainamide three times per week. From the second week, blood samples were taken once a week for antinuclear antibody (ANA) detection. At 56d after treatment, rats were sacrificed and spleens samples were collected for microarray test and histopathology examination. Frequencies of T cell subsets and B cells in rat spleen were measured to assess the effects on splenocyte. Also, 12 serum cytokines/chemokines were determined to explored the Th1/Th2 cytokine pattern after treatment. We found that ANA were makedly elevated in BN and SD rats, while the elevated appeared earlier in BN rats, and the magnitude of its increase were much higher than that of SD rats. There was no marked change in serum ANA in Lewis rats. Histopathological analysis indicated that spleen weight increased significantly both in BN and SD rats after stimulated with procainamide. No significant changes in spleen weight and lesions were observed in Lewis rats. We also found the percentage of CD86 positive cells in spleen of BN rats was significantly increased, while the percentage of CD4+CD25+ cells was decreased in BN rats. In addition, percentage of CD11b/c positive cells were decreased, and the levels of Th-2 (IL-10), Th-1 type cytokine (IFN-γ) and chemokine (IL-1β) in serum were markedly elevated both in BN and SD rats after treatment. Th-2 type cytokine (IL-4, IL-6) in serum were markedly increased only in BN rats. Furthermore, similar immune mechanisms were found in BN and SD rat, and the altered genes were mainly associated in immune response, and inflammatory response. However, the number of differentially expressed genes (DEGs) in BN rats was higher than that in SD rats. Overall, we revealed significant differences in response to autoimmunity induced by procainamide among three strains rats, the BN rats was the most sensitive one, SD rats exhibited less sensitive while Lewis resistance to procainamide. Much more pronounced of Th2-type responses and more complex DEGs involved in immune regulation and response in BN rats might contribute to its susceptible to drug-induced lupus erythematosus. Moreover, similar immune mechanisms were found between BN and SD rat, which suggesting that these changes would served as the potential bridge biomarkers to predict drug-induced autoimmune reactions among species. The results may also provide a scientic basis for the high sensitivity of BN rats in prediction immunotoxicity in preclinical studies.
2018-11-28 | GSE92500 | GEO
Project description:To investigate the variation of mRNA and lncRNA expression after using AMD3100 in rat chronic allograft nephropathy model (CAN) model, we have employed mRNA and lncRNA microarray expression profiling as a discovery platform to identify genes with the potential. CAN rat models were established using male Fisher 344 to Lewis rats. Rats in the experimental group(n=3) were treated with AMD3100 (1 mg/kg/day subcutaneously, 0–12 weeks), rats in the control group(n=3) were treated with saline. The kidney grafts were harvested 12 weeks after modeling for microarray analysis.
2018-05-08 | GSE114088 | GEO
Project description:Acute rejection episodes trigger chronic renal allograft vasculopathy. Numerous leukocytes, predominantly monocytes, accumulate in graft blood vessels during reversible acute rejection preceding chronic rejection of rat kidneys. We speculate that they contribute to transplant vasculopathy and set out to characterize them. Allogeneic renal transplantation was performed in the Fischer 344 to Lewis rat strain combination, Lewis isografts served as controls. Leukocytes were harvested by intensive perfusion of graft blood vessels and subjected to flow cytometry, quantitative RT-PCR and genome-wide transcriptional profiling. Kidneys of LEW and F344 rats were transplanted in LEW rats. Five biological replicates were performed for both isogenic and allogenic transplantation. Transcriptomes of allogenics were compared to isogenics on 5 dual-color hybridizations.
2010-09-24 | E-GEOD-18266 | biostudies-arrayexpress
Project description:Rats vary in their susceptibilities to Toxoplasma gondii infection depending on the rat strain. Compared to the T. gondii-susceptible Brown Norway (BN) rat, the Lewis (LEW) rat is extremely resistant to T. gondii. Thus, these two rat strains are ideal models for elucidating host mechanisms that are important for host resistance to T. gondii infection. Therefore, in an attempt to unravel molecular factors directing the protective early innate immune responses in the LEW rat, we performed RNA sequencing analysis of the LEW versus BN rat, with or without T. gondii infection.
2017-07-24 | GSE100203 | GEO
Project description:Chromosome 2 introgression from normotensive Brown Norway (BN) rats into hypertensive Dahl salt-sensitive (SS) background (consomic S2B) reduced blood pressure (BP) and vascular inflammation under normal salt diet (NSD). We hypothesized that BN chromosome 2 contains anti-inflammatory genes that could reduce BP elevation and vascular inflammation in rats fed NSD and high salt diet (HSD). We used chromosome 2 fragment substitutions to map chromosome 2 portion associated with vascular inflammation changes and next generation sequencing (NGS) to profile microRNAs in thoracic descending aorta of SS and congenic rats fed NSD or HSD.
2021-03-22 | GSE149515 | GEO
Project description:MicroRNAs are small non-coding RNA molecules that regulate the post-transcriptional expression of target genes. In addition to being involved in many biologic processes including development, cell differentiation, proliferation, and apoptosis, microRNAs are important regulators in innate and adaptive immune responses. Distinct sets of expressed miRNAs are found in different cell types and tissues and aberrant expression of microRNAs is associated with many disease states. MicroRNA expression was examined in a model of heterotopic heart transplantation by microarray analyses and a unique profile was detected in rejecting allogeneic transplants (BALB/C to C57BL/6) as compared to syngeneic transplants (C57BL/6 to C57BL/6). The microRNA miR-182 was significantly increased in rejecting cardiac allografts and in mononuclear cells that infiltrate the grafts. Forkhead Box (FOX) proteins are a family of important transcription factors and FOXO1 is a target of miR-182. As miR-182 increases after transplant, there is a concomitant post-transcriptional decrease in FOXO1 expression in heart allografts that is localized to both the cardiomyocytes and CD3+ T cells. The microRNA miR-182 is significantly increased in both PBMC and plasma during graft rejection suggesting potential as a biomarker of graft status. Our results identify microRNAs that may regulate alloimmune responses and graft outcomes. In total 14 microRNA microarrays data. For heart graft: each sample column corresponds to the expression profile of 3 pooled syngeneic or 3 pooled allogeneic heart grafts or 3 pooled normal heart. For graft infiltrating lymphocytes (GILs): each sample column corresponds to the expression profile of 3 pooled syngeneic or 3 pooled allogeneic GILs or 3 pooled normal PBMC.
2012-12-30 | E-GEOD-32545 | biostudies-arrayexpress