Linc-KIAA1737-2 promoted LPS-induced HK-2 cell apoptosis by regulating miR-27a-3p/TLR4/NF-κB axis.
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ABSTRACT:
SUBMITTER: Hu M
PROVIDER: S-EPMC8360891 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)-dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1β, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.
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Project description:ObjectiveThe aim of this study was to investigate the anti-inflammatory effect of Rosiglitazone (RGZ) on lipopolysaccharide (LPS) -induced Endometritis and explore its possible mechanism.MethodsThe preventive and therapeutic effects of RGZ on Endometritis were studied in vivo and in vitro. A total of 40 female C57BL/6 mice were randomly divided into the following 4 groups: RGZ+LPS, RGZ control, LPS and DMSO control. The mice uterine tissue sections were performed with HE and immunohistochemical staining. Human endometrial stromal cells (HESCs) were cultured, and different concentrations of LPS stimulation groups and RGZ and/or a TLR4 signaling inhibitor TAK-242 pretreatment +LPS groups were established to further elucidate the underlying mechanisms of this protective effect of RGZ.ResultsThe HE results in mice showed that RGZ+LPS group had less tissue loss than LPS group. Immunohistochemical staining (IHC) results showed that the expression of TLR4 after RGZ treatment was significantly lower than that in LPS group. These findings suggested that RGZ effectively improves the pathological changes associated with LPS-induced endometritis by inhibiting TLR4. Reverse transcription-polymerase chain reaction and western blot analysis demonstrated that RGZ pretreatment suppresses the expression of Toll-like receptor 4 (TLR4) and its downstream activation of nuclear factor-κB (NF-κB). In vitro, RGZ inhibited LPS-stimulated expression of proinflammatory cytokines in a dose-dependent manner and also downregulated LPS induced toll-like receptor 4 (TLR4) expression and inhibited phosphorylation of LPS-induced nuclear transcription factor-kappa B (NF-κB) P65 protein.ConclusionsThese results suggest that RGZ may inhibit LPS-induced endometritis through the TLR4-mediated NF-κB pathway.
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Project description:Catalpol is the main active ingredient of an extract from Radix rehmanniae, which in a previous study showed a protective effect against various types of tissue injury. However, a protective effect of catalpol on uterine inflammation has not been reported. In this study, to investigate the protective mechanism of catalpol on lipopolysaccharide (LPS)-induced bovine endometrial epithelial cells (bEECs) and mouse endometritis, in vitro and in vivo inflammation models were established. The Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway and its downstream inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), western blot (WB), and immunofluorescence techniques. The results from ELISA and qRT-PCR showed that catalpol dose-dependently reduced the expression of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6, and chemokines such as C-X-C motif chemokine ligand 8 (CXCL8) and CXCL5, both in bEECs and in uterine tissue. From the experimental results of WB, qRT-PCR, and immunofluorescence, the expression of TLR4 and the phosphorylation of NF-κB p65 were markedly inhibited by catalpol compared with the LPS group. The inflammatory damage to the mouse uterus caused by LPS was greatly reduced and was accompanied by a decline in myeloperoxidase (MPO) activity. The results of this study suggest that catalpol can exert an anti-inflammatory impact on LPS-induced bEECs and mouse endometritis by inhibiting inflammation and activation of the TLR4/NF-κB signaling pathway.
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Project description:Our results showed that both circRNA and mRNA profiles are different from those of the sham group. A significant upregulation of circ-Phkb was observed in NR8383 cells and rats exposed to LPS. When circ-Phkb expression was reduced in NR8383 cells, apoptosis and inflammation were greatly reduced, and cell proliferation was increased, while overexpression of circ-Phkb have the opposite effect. In terms of mechanism, circ-Phkb suppression inhibits CCL2 expression via TLR4/MyD88/NF-κB pathway.
2024-02-07 | GSE226036 | GEO
Project description:Sepsis is a severe inflammatory disease caused by infection that can lead to multiple organ failure. Acute kidney injury (AKI) is considered to be a major cause of septic mortality in infected organs. Previous studies have revealed that non-coding RNAs are involved in AKI, but the underlying mechanisms are mostly unknown. The present study aimed to explore the role of long non-coding RNA plasmacytoma variant translocation gene 1 (lncRNA PVT1) in lipopolysaccharide (LPS)-induced acute kidney injury and the underlying mechanism. In the present study, reverse transcription-quantitative PCR analysis indicated that, in HK-2 cells treated with LPS, the mRNA expression levels of lncRNA PVT1 and oxidative stress responsive kinase 1 (OXSR1) were upregulated, and the expression of microRNA (miR)-27a-3p was downregulated. Furthermore, LPS treatment could promote the secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6, inhibit cell proliferation and induce apoptosis, which was rescued by PVT1 knockdown. Dual-luciferase reporter assay, RIP assay and pull-down assay results demonstrated that miR-27a-3p may be a target miR of PVT1, and that OXSR1 is the target gene of miR-27a-3p. Moreover, it was found that miR-27a-3p overexpression decreased the secretion of TNF-α and IL-6, promoted cell proliferation and inhibited apoptosis in LPS-treated HK-2 cells, which could be reversed by OXSR1 overexpression. Therefore, the present results indicated that lncRNA PVT1 regulated inflammatory cytokine secretion, cell proliferation and apoptosis by targeting miR-27a-3p, and modulating OXSR1 expression in LPS-induced HK-2 cells.
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Project description:BackgroundThis research sought to elucidate the effects of peroxiredoxin 6 (PRDX6) on the biological processes in diabetic nephropathy (DN) and to identify the underlying regulatory mechanism related to toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling.MethodsTo induce an in vitro DN cellular model, human kidney 2 (HK-2) cells were treated with high glucose (HG). The mitochondrial membrane potential, adenosine triphosphate level, reactive oxygen species generation, and oxidative stress of the cells were then evaluated. After the PRDX6 level had been determined, the effects of its overexpression on the mitochondrial membrane potential, adenosine triphosphate level, reactive oxygen species generation, and oxidative stress of the cells were assessed. Next, cytochrome c expression, cell viability, cell apoptosis, the inflammatory level, and the TLR4/NF-κB signaling-related factors were assessed. After the addition of the TLR4 activator CRX-527 or the NF-κB activator phorbol 12-myristate 13-acetate (PMA), cell viability, cell apoptosis and the inflammatory level were evaluated again.ResultsThe results revealed that HG exposure triggered mitochondrial dysfunction and oxidative stress and decreased PRDX6 expression in the HK-2 cells. PRDX6 elevation exacerbated cell viability while alleviating mitochondrial membrane potential loss, oxidative stress, apoptosis, and inflammation in the HG-treated HK-2 cells. Further, PRDX6 inhibited HG-induced TLR4/NF-κB activation. The administration of CRX-527 or PMA reversed the effects of PRDX6 on the cell viability, apoptosis, and inflammation of the HG-exposed HK-2 cells.ConclusionsTo conclude, PRDX6 appears to protect HG-exposed HK-2 cells against inflammation and apoptosis by inhibiting TLR4/NF-κB signaling.
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