Calycosin inhibited MIF-mediated inflammatory chemotaxis of macrophages to ameliorate ischemia reperfusion-induced acute kidney injury
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ABSTRACT:
PROVIDER: PRJNA1037013 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26803335_1.fastq.gz | Fastqsanger.gz | |||
| SRR26803335_2.fastq.gz | Fastqsanger.gz | |||
| SRR26803336_1.fastq.gz | Fastqsanger.gz | |||
| SRR26803336_2.fastq.gz | Fastqsanger.gz | |||
| SRR26803337_1.fastq.gz | Fastqsanger.gz |
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Project description:Acute kidney disease caused by ischemia-reperfusion (IRI-AKI) is characterized by ectopic inflammation and tubular injury, in which macrophage infiltration and inflammatory activation play a critical pathogenic role. Calycosin is an active flavone from the root of Astragalus membranaceus and shows anti-inflammatory effects in various diseases. In this study, we investigated the renoprotective role of calycosin against IRI-AKI and the underlying mechanism. Our results showed that calycosin treatment reduced the levels of serum creatinine and urea nitrogen along with attenuated tubular necrosis and cast formation in IRI-AKI mice. Calycosin significantly suppressed the activation of NF-κB signaling and the expression of inflammatory mediators IL-1β and TNF-α in IRI-AKI kidneys. In vitro, calycosin inhibited LPS-induced inflammatory activation in RAW 264.7 cells. Interestingly, RNA-seq revealed that calycosin remarkably down-regulated chemotaxis-related pathways in RAW 264.7 cells. Among the differentially expressed genes, Ccl2/MCP-1, a critical chemokine mediating macrophage inflammatory chemotaxis, was down-regulated in both LPS-stimulated RAW 264.7 cells and IRI-AKI kidneys. Consistently, calycosin treatment attenuated macrophage infiltration in the IRI-AKI kidneys. Importantly, in combination with target prediction, molecular docking, and surface plasmon resonance, we showed that calycosin can directly bind to macrophage migration inhibitory factor (MIF). Functionally, calycosin abrogated MIF-stimulated NF-κB signaling activation and Ccl2 expression and MIF-mediated chemotaxis in RAW 264.7 cells without influencing its expression. Collectively, calycosin protects from IRI-AKI by suppressing MIF-mediated macrophage inflammatory chemotaxis. Calycosin could be a promising candidate medicine for clinical treatment of IRI-AKI.
2024-07-28 | GSE247263 | GEO
Project description:Background: Hepatic ischemia–reperfusion (I/R) injury is a major complication leading to surgical failures in liver resection, transplantation, and hemorrhagic shock. The role of cytokine macrophage migration inhibitory factor (MIF) in hepatic I/R injury is unclear. Methods: We examined changes of MIF expression in mice after hepatic I/R surgery and hepatocytes challenged with hypoxia–reoxygenation (H/R) insult. Subsequently, MIF global knock-out mice and mice with adeno-associated-virus (AAV)-delivered MIF overexpression were subjected to hepatic I/R injury. Hepatic histology, the inflammatory response, apoptosis and oxidative stress were monitored to assess liver damage. The molecular mechanisms of MIF function were explored in vivo and in vitro. Results: MIF was significantly upregulated in the serum whereas decreased in liver tissues of mice after hepatic I/R injury. MIF knock-out effectively attenuated I/R -induced liver inflammation, apoptosis and oxidative stress in vivo and in vitro, whereas MIF overexpression significantly aggravated liver injury. Via RNA-seq analysis, we found a significant decreased trend of MAPK pathway in MIF knock-out mice subjected hepatic I/R surgery. Using the apoptosis signal-regulating kinase 1 (ASK1) inhibitor NQDI-1 we determined that, mechanistically, the protective effect of MIF deficiency on hepatic I/R injury was dependent on the suppressing of the ASK1-JNK/P38 signaling pathway. Moreover, we found MIF inhibitor ISO-1 alleviate hepatic I/R injury in mice. Conclusion: Our results confirm that MIF deficiency suppresses the ASK1-JNK/P38 pathway and protects the liver from I/R -induced injury. Our findings suggest MIF as a novel biomarker and therapeutic target for the diagnosis and treatment of hepatic I/R injury.. We then performed gene expression profiling analysis using data obtained from RNA-seq of 6 different liver tissues of mice subjected to hepatic I/R injury.
2022-09-28 | GSE212508 | GEO
Project description:The aim of this experiment was to investigate the role of MIF during wound healing using BALB/C MIF null mice and in the context of reduced estrogen-associated impaired healing using ovariectomized mice (a mouse model of age-associated delayed healing). Ageing is associated with delayed cutaneous wound healing resulting from reduced estrogen levels. Macrophage migration inhibitory factor (MIF - NCBI RefSeq: NM_010798) is thought to mediate the effects of estrogen on wound healing. Gene expression was compared between wounds from ovariectomized MIF null mice and controls.
2005-11-05 | E-MEXP-209 | biostudies-arrayexpress
Project description:siRNA-mediated knockdown of MIF expression in HEK293 cells resulted in inhibition of cell proliferation and cell cycle progress. The microarray study of MIF KD cells reveald knockdown of MIF would lead to extensive changes in gene expression profiles which may elucidate the molecular mechanism of MIF siRNA-mediated inhibition of cell cycle and cell proliferation. Keywords: The whole-genome expression analysis in MIF knockdown cells and the control cells HEK293 cells were transfected MIF siRNA (50pmol/ml & 100pmol/ml) or control RNA using LipofectamineTM 2000 reagent and re-incubated for 24 hours.At the designed time point, totol RNA was isolated from the different treated cells.The normal cells were used as control.
2009-11-02 | E-GEOD-10241 | biostudies-arrayexpress
Project description:We identified differentially expressed microRNAs between MIF-high and MIF-low tumor groups. These microRNAs were then investigated for their potential downstream targets using an integrative strategy, which combines miR-Walk target prediction module and mRNA expression array data to identify key MIF-induced signalling pathways driving tumor progresion and disease aggressiveness. Genes that associated with prognostic significance was then subjected to mechanistic study. miRNA expression profiling of 69 pancreatic ductual adenocarcinoma was performed in two sets. The batch effect between the two sets of data was removed using Partek Genomic Suite
2016-06-01 | E-GEOD-62498 | biostudies-arrayexpress
Project description:siRNA-mediated knockdown of MIF expression in HEK293 cells resulted in inhibition of cell proliferation and cell cycle progress. The microarray study of MIF KD cells reveald knockdown of MIF would lead to extensive changes in gene expression profiles which may elucidate the molecular mechanism of MIF siRNA-mediated inhibition of cell cycle and cell proliferation. Keywords: The whole-genome expression analysis in MIF knockdown cells and the control cells
2009-11-03 | GSE10241 | GEO
Project description:We identified differentially expressed microRNAs between MIF-high and MIF-low tumor groups. These microRNAs were then investigated for their potential downstream targets using an integrative strategy, which combines miR-Walk target prediction module and mRNA expression array data to identify key MIF-induced signalling pathways driving tumor progresion and disease aggressiveness. Genes that associated with prognostic significance was then subjected to mechanistic study.
2016-06-01 | GSE62498 | GEO
Project description:Lasting B-cell persistence depends on survival signals that are transduced by cell surface receptors. Here, we describe a novel biological mechanism essential for survival and homeostasis of normal peripheral mature B cells and chronic lymphocytic leukemia (CLL) cells, regulated by the heparin-binding cytokine, midkine (MK), and its proteoglycan receptor, the receptor-type tyrosine phosphatase zeta (RPTPζ). We demonstrate that MK initiates a signaling cascade leading to B cell survival, by binding to RPTPζ. In mice lacking PTPRZ, the proportion and number of the mature B cell population is reduced. Our results emphasize a unique and critical function for MK signaling in the previously described MIF/CD74 induced survival pathway. Stimulation of CD74 with MIF leads to c-Met activation, resulting in elevation of MK expression in both normal mouse splenic B and CLL cells. Our results indicate that MK and RPTPζ are important regulators of the B cell repertoire. These findings could pave the way towards understanding the mechanisms shaping B cell survival, and suggest novel therapeutic strategies based on the blockade of the midkine/RPTPζ-dependent survival pathway. 2 samples were incubated with or without MIF.
2011-11-01 | E-GEOD-33352 | biostudies-arrayexpress
Project description:BackgroundHypoxia preconditioning has been proven to be an effective method to enhance the therapeutic action of mesenchymal stem cells (MSCs). However, the beneficial effects of hypoxic MSCs in ischemia/reperfusion (I/R) lung injury have yet to be investigated. In this study, we hypothesized that the administration of hypoxic MSCs would have a positive therapeutic impact on I/R lung injury at molecular, cellular, and functional levels.MethodsI/R lung injury was induced in isolated and perfused rat lungs. Hypoxic MSCs were administered in perfusate at a low (2.5×105 cells) and high (1×106 cells) dose. Rats ventilated with a low tidal volume of 6 ml/kg served as controls. Hemodynamics, lung injury indices, inflammatory responses and activation of apoptotic pathways were determined.ResultsI/R induced permeability pulmonary edema with capillary leakage and increased levels of reactive oxygen species (ROS), pro-inflammatory cytokines, adhesion molecules, cytosolic cytochrome C, and activated MAPK, NF-κB, and apoptotic pathways. The administration of a low dose of hypoxic MSCs effectively attenuated I/R pathologic lung injury score by inhibiting inflammatory responses associated with the generation of ROS and anti-apoptosis effect, however this effect was not observed with a high dose of hypoxic MSCs. Mechanistically, a low dose of hypoxic MSCs down-regulated P38 MAPK and NF-κB signaling but upregulated glutathione, prostaglandin E2, IL-10, mitochondrial cytochrome C and Bcl-2. MSCs infused at a low dose migrated into interstitial and alveolar spaces and bronchial trees, while MSCs infused at a high dose aggregated in the microcirculation and induced pulmonary embolism.ConclusionsHypoxic MSCs can quickly migrate into extravascular lung tissue and adhere to other inflammatory or structure cells and attenuate I/R lung injury through anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms. However, the dose of MSCs needs to be optimized to prevent pulmonary embolism and thrombosis.
| S-EPMC5678873 | biostudies-literature
Project description:The presence of activated pancreatic stellate cells (PSCs) in the pancreatic ductal adenocarcinoma (PDAC) microenvironment plays a significant role in cancer progression. Macrophage migration inhibitory factor (MIF) is overexpressed in PDAC tissues and expressed by both cancer and stromal cells. The expression status of MIF and its receptors in PDAC- associated fibroblasts or PSCs and its pathophysiological roles are yet to be elucidated. The next-generation sequencing technique was adapted to check the effect of MIF absence on the expression of other genes in mice (mPSCs).
2022-09-28 | E-MTAB-9392 | biostudies-arrayexpress