Single-cell RNA sequencing reveals roles of fibroblasts during intestinal injury and repair in rats with severe acute pancreatitis
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE244963 | GEO | 2023/12/20
REPOSITORIES: GEO
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Project description:Long non-coding RNAs (lncRNAs) reportedly contribute to disease pathogenesis and drug treatment effects. Both emodin and dexamethasone (DEX) have been used for the treatment of severe acute pancreatitis-associated acute lung injury (SAP-ALI). However, lncRNA regulation networks related to SAP-ALI pathogenesis and drug treatment are unreported. In this study, lncRNAs and mRNAs in the lung tissue of SAP-ALI and control rats, with or without drug treatment (emodin or DEX), were assessed by RNA sequencing. Results showed that both emodin and DEX were therapeutic for SAP-ALI and that mRNA and lncRNA levels differed between untreated and treated SAP-ALI rats. Gene expression profile relationships for emodin treated and control rats were higher than DEX treated and untreated animals. By comparison of control and SAP-ALI animals, more upregulated than downregulated mRNAs and lncRNAs were observed with emodin treatment. For DEX treatment, more downregulated than upregulated mRNAs and lncRNAs were observed. Functional analysis demonstrated both upregulated mRNA and co-expressed genes with upregulated lncRNAs were enriched in inflammatory and immune response pathways. Further, emodin associated lncRNAs and mRNAs co-expressed modules were different from those associated with DEX. Quantitative polymerase chain reaction demonstrates that selected lncRNA and mRNA co-expressed modules were different in the lung tissue of emodin and DEX treated rats. Also, emodin had different effects compared to DEX on the co-expression network of lncRNAs Rn60_7_1164.1 and AABR07062477.2 for the blue lncRNA module and Nrp1 for the green mRNA module. In conclusion, this study provides evidence that emodin may be a suitable alternative or complementary medicine for treatment of SAP-ALI.
2021-01-03 | GSE151572 | GEO
Project description:Endocannabinoid 2-arachidonoylglycerol (2-AG) is an anti-nociceptive lipid that is inactivated through cellular uptake and subsequent catabolism by monoacylglycerol lipase (MAGL). In this study, we investigated the effects of MAGL inhibition on intestinal permeability and explored the possible mechanism. A rat model of severe acute pancreatitis (SAP) was established. Rats were divided into three groups according to treatment. We analyzed intestinal permeability to fluorescein isothiocyanate-dextran and the levels of inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and 2-AG. Hematoxylin and eosin staining was used to assess histological tissue changes. In vivo intestinal permeability was evaluated by transmission electron microscopy. We obtained ileum tissues, extracted total RNA, and applied RNA-sequencing. Sequencing data were analyzed by bioinformatics. Inflammatory factor levels were higher, while 2-AG levels were lower in the SAP group compared with the control group. Administration of JZL184 to rats with SAP increased the levels of 2-AG and lowered the levels of IL-6 and TNF-α. Notably, intestinal permeability was improved by JZL184 as demonstrated by fluorescein isothiocyanate-dextran measurement, hematoxylin and eosin staining, and transmission electron microscopy. RNA-sequencing showed significant transcriptional differences in SAP and JZL184 groups compared with the control group. KEGG analysis showed that the up- or downregulated genes in multiple comparison groups were enriched in two pathways, focal adhesion and PI3K-Akt signaling pathways. Differential alternative splicing (AS) genes, such as Myo9b, Lsp1, and Git2, have major functions in intestinal diseases. A total of 132 RNA-binding proteins (RBPs) were screened by crossing the identified abnormally expressed genes with the reported RBP genes. Among them, Hnrnpdl coexpressed the most AS events as the main RBP. MAGL inhibition improved intestinal mucosal barrier injury in SAP rats and induced a large number of differentially expressed genes and alternative splicing events. Hnrnpdl might play an important role in improving intestinal mucosal barrier injury by affecting alternative splicing events.
2022-03-18 | GSE197930 | GEO
Project description:To investigate the mechanism of electrical stimulation in the repair of spinal cord injury, we established a rat model of spinal cord injury. Then, we used RNA-SEQ data obtained from ES treatment and 6 different rat models of spinal cord injury for gene expression profile analysis.
2023-07-01 | GSE214291 | GEO
Project description:[This corrects the article DOI: 10.1155/2016/4592346.].
| S-EPMC5818923 | biostudies-literature
Project description:Picroside II is an important ingredient agent in Traditional Chinese medicine and hoped to reduce hepatocellular injury caused by severe acute pancreatitis (SAP). An SAP-induced hepatocellular injury model was established in rats by using pentobarbital sodium. 27 rats were divided into 3 groups: the sham group (SG), model group (MG), and Picroside groups (PG). SAP-induced hepatocellular injury was assessed using hematoxylin and eosin staining. We measured hepatocellular enzymes (amylase (AMY), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)), oxidative stress factors (superoxidase dismutase (SOD) and malondialdehyde (MDA)), and inflammatory factors (tumor necrosis factor α (TNF-α), interleukin- (IL-) 6, and IL-10), apoptotic factors (BAX and cleaved caspase 3), and inflammatory signaling (Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), p-JAK2, and p-STAT3) in hepatocellular tissues. The SAP-induced hepatocellular injury model was successfully established. Picroside II treatment repaired hepatocellular injury by reducing the activities of AMY, ALT, and AST; reducing the levels of MDA, TNF-α, IL-1, IL-6, p-JAK2, p-STAT3, BAX, and cleaved caspase 3; and increasing the levels of SOD and IL-10. Picroside II exerted protective function for the SAP-induced hepatocellular injury model. Picroside II improved SAP-induced hepatocellular injury and antioxidant and anti-inflammatory properties by affecting JAK2/STAT3 phosphorylation signaling.
| S-EPMC8337114 | biostudies-literature
Project description:The aim of the present study was to investigate the effect of curcumin on acute renal injury in a rat model of severe acute pancreatitis (SAP). A SAP model with acute kidney injury was established in rats by retrograde injection of 5% sodium taurocholate into the pancreatic duct. The serum amylase, creatinine (Cr) and blood urea nitrogen (BUN) levels in rats were measured. Hematoxylin and eosin staining was used to assess pancreatic and renal histological changes. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured using ELISA kits. Renal protein levels of Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway components were determined by western blot assay. The results showed that curcumin significantly decreased serum amylase, Cr and BUN levels, and alleviated pancreatic and renal histological changes in SAP rats. Furthermore, curcumin markedly decreased serum TNF-α and IL-6 levels and downregulated renal protein levels of JAK2/STAT3 pathway components. These results proved that curcumin ameliorates acute renal injury in a rat model of SAP. The molecular mechanism of its effect may be associated with the suppression of the JAK2/STAT3 pathway to reduce TNF-α and IL-6 levels in SAP-induced acute renal injury. Therefore, the findings of the present study revealed the potential use of curcumin for the prevention and treatment of SAP and the associated renal injury.
| S-EPMC5526141 | biostudies-other
Project description:The traditional Chinese formula Da-Cheng-Qi-decoction (DCQD) has been used to treat acute pancreatitis for decades. DCQD could ameliorate the disease severity and the complications of organ injuries, including those of the liver and lungs. However, the pharmacological effects in the kidney, a target organ, are still unclear. This study aimed to investigate the herbal tissue pharmacology of DCQD for acute kidney injury (AKI) in rats with severe acute pancreatitis (SAP).Rats were randomly divided into the sham-operation group (SG), the model group (MG) and the low-, medium- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Sodium taurocholate (3.5%) was retrogradely perfused into the biliopancreatic duct to establish the model of SAP in rats. Different doses of DCQD were administered to the treatment groups 2 h after the induction of SAP. The major components of DCQD in kidney tissues were detected by HPLC-MS/MS. Inflammatory mediators in the kidney tissues, as well as serum creatinine (Scr), blood urea nitrogen (BUN) and pathologic scores, were also evaluated.Ten components of DCQD were detected in the kidneys of the treatment groups, and their concentrations increased dose-dependently. Compared with the SG, the levels of inflammatory mediators, Scr, BUN and pathological scores in the MG were obviously increased (p?<?0.05). The high dose of DCQD showed a maximal effect in downregulating the pro-inflammatory mediators interleukin-6 (IL)-6 and tumour necrosis factor-? (TNF-?), upregulating anti-inflammatory mediators IL-4 and IL-10 in the kidney and alleviating the pathological damages. DCQD decreased the pancreas and kidney pathological scores of rats with SAP, especially in the HDG (p?<?0.05). Compared with the MG, the level of Scr in the HDG was significantly decreased (p?<?0.05).DCQD ameliorated AKI in rats with SAP via regulating the inflammatory response, which might be closely related to the distribution of its components in the kidney.
| S-EPMC6045888 | biostudies-other
Project description:The rat tendon injury models were established and divided into three groups: normal control group, injury model group, and celecoxib + lactoferrin treatment group. Then, RNA sequencing and differential expression analysis were performed for samples from injury model group and celecoxib + lactoferrin treatment group on day 14. Next, autophagy/hypoxia/ferroptosis/pyroptosis-related genes retrieved from the corresponding databases and related literatures were downloaded to obtain the genes associated with autophagy/hypoxia/ferroptosis/pyroptosis. Subsequently, functional annotation, protein-protein interaction (PPI) network and transcriptional regulatory network construction for these genes were performed.
2022-11-20 | GSE201161 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE26695: Transcriptomic response of murine liver to severe injury and hemorrhagic shock: Affymetrix portion of dual platform GSE26696: Transcriptomic response of murine liver to severe injury and hemorrhagic shock: CodeLink portion of dual platform Refer to individual Series
2011-01-24 | E-GEOD-26697 | biostudies-arrayexpress
Project description:BACKGROUND:Severe acute pancreatitis (SAP) is an acute abdominal disease characterized by pancreatic necrosis and systemic disease. In a previous study, we showed that bone marrow-derived mesenchymal stem cells (BMSCs) can reduce SAP by secreting microRNA (miR)-9; however, the underlying mechanism remains unclear. The present study investigated the mechanism underlying BMSC-induced pancreatic regeneration. METHODS:BMSCs were isolated, and miR-9 modified/antagonized BMSCs (pri-miR-9-BMSCs/TuD-BMSCs) were generated and injected into SAP rats. The levels of inflammatory cytokines and histopathologic changes were examined using ELISA and H&E staining. Angiogenesis was analyzed by qRT-PCR, western blotting, and immunohistochemistry. Cell function tests, dual luciferase reporter assays, cell co-culture, western blotting, and cell tracing were used to explore the mechanisms underlying miR-9 induced angiogenesis. RESULTS:Pri-miR-9-BMSCs induced angiogenesis in SAP rats (Ang-1↑, TIE-2↑, and CD31↑) and repaired damaged vascular endothelial cells (VECs) in vitro, promoting angiogenesis (Ang-1↑, TIE-2↑, PI3K↑, AKT↑, p-AKT↑, CD31↑, and CD34↑). Pri-miR-9-BMSCs released miR-9 into VECs or injured pancreatic tissue, targeting the VE-cadherin gene and promoting PI3K/AKT signaling to treat SAP (VE-cadherin↓, β-catenin↓, PI3K↑, p-AKT↑), whereas antagonizing miR-9 in BMSCs did not alleviate or aggravated SAP. CONCLUSIONS:Pri-miR-9-BMSCs can repair injured pancreatic tissue by secreting miR-9 and promoting angiogenesis.
| S-EPMC6202805 | biostudies-other