Similar Datasets
Project description:This study depicts a novel mechanism by which CVC alleviates liver fibrosis by restoring the immune cell landscape. CVC can inhibit profibrotic gene transcription via inactivating the CCR2-STAT1/NF&B/ERK signaling pathways.
2023-08-31 | GSE218497 | GEO
Project description:This study depicts a novel mechanism by which CVC alleviates liver fibrosis by restoring the immune cell landscape. CVC can inhibit profibrotic gene transcription via inactivating the CCR2-STAT1/NF&B/ERK signaling pathways.
2023-08-31 | GSE218496 | GEO
Project description:Cenicriviroc reduces liver fibrosis by restoring the immune cell landscape via inactivating STAT1/NF&B/ERK signaling pathways
| PRJNA903938 | ENA
Project description:Cenicriviroc reduces liver fibrosis by restoring the immune cell landscape via inactivating STAT1/NF&B/ERK signaling pathways [prevention_RNA-seq]
| PRJNA903940 | ENA
Project description:Cenicriviroc reduces liver fibrosis by restoring the immune cell landscape via inactivating STAT1/NF&B/ERK signaling pathways [treatment_scRNA-seq]
| PRJNA903941 | ENA
Project description:Introduction and rationalePrevious studies have shown that delayed neutrophil apoptosis is associated with chronic airway diseases. Leptin is an adipocyte-derived hormone that acts as a regulator of energy homeostasis and food intake. Emerging evidence suggests that leptin can regulate immune responses including the release of proinflammatory cytokines and protection of inflammatory cells from apoptosis. Serum leptin is increased during allergic reactions in the airways. However, the expression and function of leptin receptor in neutrophils isolated from children is not known.MethodsFlow cytometry was used to detect leptin receptor expression in neutrophils isolated from allergic asthmatic (n?=?14), allergic non asthmatic (n?=?21), non allergic asthmatic (n?=?7) and healthy children (n?=?23); confocal laser scanning microscopy combined with immunofluorescence was performed to detect intracellular pool of leptin receptor; Annexin-V/PI staining and caspase 3 activity was used to determine neutrophil survival. Pharmacological inhibitors were utilized to understand the role of MAPK and NF-?B pathway in leptin-induced neutrophil survival.Results and conclusionA heterogeneous leptin receptor expression was observed on neutrophils isolated from children. Neutrophils isolated from healthy children expressed more leptin receptor than those from allergic asthmatic (P<0.05) but not allergic non-asthmatic (P>0.05) or non-allergic asthmatic children (n?=?7, P>0.05). Neutrophils isolated from children express an intracellular pool of leptin receptor that was mobilized to the cell surface upon GM-CSF stimulation. Finally, leptin exhibited anti-apoptotic properties on neutrophils via NF-?B and MEK1/2 MAPK pathway. Collectively, our data suggest that leptin may enhance airway inflammation by promoting neutrophil survival.
| S-EPMC3561393 | biostudies-literature
Project description:PurposeWe examined whether anlotinib can attenuate folic acid-induced and unilateral ureteral obstruction-induced renal fibrosis and explored the underlying antifibrotic mechanism.Materials and methodsWe have evaluated the effects of anlotinib on folic acid-induced and unilateral ureteral obstruction-induced renal fibrosis in mice through in vivo experiments of unilateral ureteral obstruction or folic acid-induced interstitial fibrosis and in vitro models of transforming growth factor-β1 induced HK-2 human renal proximal tubule cells. Serum renal function parameters and inflammatory cytokine levels were measured, and histological changes of renal injury and fibrosis were analyzed by HE staining and immunohistochemistry. Immunohistochemistry and Western blotting were used to determine the mechanism of action of anlotinib in ameliorating renal fibrosis.ResultsAnlotinib improved proteinuria and reduced renal impairment in folic acid-induced mouse models of renal fibrosis. Anlotinib reduced tubular injury, deposition of tubular extracellular matrix, and expression of alpha-smooth muscle actin, transforming growth factor-β1, and cytosolic inflammatory factors compared with controls.ConclusionsAnlotinib ameliorated renal function, improved extracellular matrix deposition, reduced protein levels of epithelial-mesenchymal transition markers, and decreased cellular inflammatory factors. Anlotinib reduced renal injury and fibrosis by inhibiting the transforming growth factor-β1 signaling pathway through AKT and ERK channels.
| S-EPMC9966823 | biostudies-literature
Project description:Azithromycin is effective at controlling exaggerated inflammation and slowing the long-term decline of lung function in patients with cystic fibrosis. We previously demonstrated that the drug shifts macrophage polarization toward an alternative, anti-inflammatory phenotype. In this study we investigated the immunomodulatory mechanism of azithromycin through its alteration of signaling via the NF-κB and STAT1 pathways. J774 murine macrophages were plated, polarized (with IFN-γ, IL-4/-13, or with azithromycin plus IFN-γ) and stimulated with LPS. The effect of azithromycin on NF-κB and STAT1 signaling mediators was assessed by Western blot, homogeneous time-resolved fluorescence assay, nuclear translocation assay, and immunofluorescence. The drug's effect on gene and protein expression of arginase was evaluated as a marker of alternative macrophage activation. Azithromycin blocked NF-κB activation by decreasing p65 nuclear translocation, although blunting the degradation of IκBα was due, at least in part, to a decrease in IKKβ kinase activity. A direct correlation was observed between increasing azithromycin concentrations and increased IKKβ protein expression. Moreover, incubation with the IKKβ inhibitor IKK16 decreased arginase expression and activity in azithromycin-treated cells but not in cells treated with IL-4 and IL-13. Importantly, azithromycin treatment also decreased STAT1 phosphorylation in a concentration-dependent manner, an effect that was reversed with IKK16 treatment. We conclude that azithromycin anti-inflammatory mechanisms involve inhibition of the STAT1 and NF-κB signaling pathways through the drug's effect on p65 nuclear translocation and IKKβ.
| S-EPMC6684391 | biostudies-literature
Project description:BackgroundThe aberrant expression of myotubularin-related protein 2 (MTMR2) has been found in some cancers, but little is known about the roles and clinical relevance. The present study aimed to investigate the roles and clinical relevance of MTMR2 as well as the underlying mechanisms in gastric cancer (GC).MethodsMTMR2 expression was examined in 295 GC samples by using immunohistochemistry (IHC). The correlation between MTMR2 expression and clinicopathological features and outcomes of the patients was analyzed. The roles of MTMR2 in regulating the invasive and metastatic capabilities of GC cells were observed using gain-and loss-of-function assays both in vitro and in vivo. The pathways involved in MTMR2-regulating invasion and metastasis were selected and identified by using mRNA expression profiling. Functions and underlying mechanisms of MTMR2-mediated invasion and metastasis were further investigated in a series of in vitro studies.ResultsMTMR2 was highly expressed in human GC tissues compared to adjacent normal tissues and its expression levels were significantly correlated with depth of invasion, lymph node metastasis, and TNM stage. Patients with MTMR2high had significantly shorter lifespan than those with MTMR2low. Cox regression analysis showed that MTMR2 was an independent prognostic indicator for GC patients. Knockdown of MTMR2 significantly reduced migratory and invasive capabilities in vitro and metastases in vivo in GC cells, while overexpressing MTMR2 achieved the opposite results. MTMR2 knockdown and overexpression markedly inhibited and promoted the epithelial-mesenchymal transition (EMT), respectively. MTMR2 mediated EMT through the IFNγ/STAT1/IRF1 pathway to promote GC invasion and metastasis. Phosphorylation of STAT1 and IRF1 was increased by MTMR2 knockdown and decreased by MTMR2 overexpression accompanying with ZEB1 down-regulation and up-regulation, respectively. Silencing IRF1 upregulated ZEB1, which induced EMT and consequently enhanced invasion and metastasis in GC cells.ConclusionsOur findings suggest that MTMR2 is an important promoter in GC invasion and metastasis by inactivating IFNγ/STAT1 signaling and may act as a new prognostic indicator and a potential therapeutic target for GC.
| S-EPMC6528261 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is a type of idiopathic interstitial pneumonia with a poor clinical prognosis. Increasing evidence has demonstrated that epithelial-mesenchymal transition (EMT) contributes to the production of pathogenic myofibroblasts and plays a pivotal role in the development of pulmonary fibrosis. Mannan-binding lectin (MBL) is a soluble calcium-dependent complement molecule. Several studies have reported associations between serum MBL levels and lung diseases; however, the effect of MBL on IPF remains unknown. The present study observed aggravated pulmonary fibrosis in bleomycin-treated MBL-/- mice compared with their wild-type counterparts. Lung tissues from bleomycin-treated MBL-/- mice displayed a more severe EMT phenotype. In vitro studies determined that MBL inhibited the EMT process through attenuating store-operated calcium entry (SOCE) signaling. It was further demonstrated that MBL promoted the ubiquitination of Orai1, an essential component of SOCE, via pyruvate dehydrogenase kinase 1 (PDK1)-serum glucocorticoid-regulated kinase 1 signaling. PDK1 inhibition abolished the MBL-mediated regulation of SOCE activity and the EMT process. Notably, biochemical analysis showed that MBL interacted with PDK1 and contributed to PDK1 ubiquitination. In summary, the present findings suggested that MBL limited the EMT phenotype in human alveolar epithelial cells through regulation of SOCE, and MBL could be recognized as a potential therapeutic target for IPF.
| S-EPMC10643902 | biostudies-literature