Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MiR-374a Regulates Inflammatory Response in Diabetic Nephropathy by Targeting MCP-1 Expression.

ABSTRACT: The microRNA (mir)-374a has been implicated in several types of human cancer; however, its role in diabetic nephropathy (DN) remains unclear. Monocyte chemoattractant protein (MCP)-1 is a chemokine that recruits macrophages to inflammatory sites and is important for the development and progression of DN. However, the relationship between miR-374a and MCP-1 in DN is unknown. We addressed this in the present study by examining the expression of these factors in kidney tissue samples from DN patients and through loss- and gain-of-function experiments using HK2 human renal tubular epithelial cells. We found that miR-374a was downregulated whereas MCP-1 was upregulated in DN tissue. A bioinformatics analysis revealed that MCP-1 is a putative target of miR-374a. To confirm this relationship, HK2 cells treated with normal glucose (5.6 mmol/l D-glucose), high glucose (HG) (30 mmol/l D-glucose), or high osmotic pressure solution (5.6 mmol/l D-glucose + 24.4 mmol/l D-mannitol) were transfected with miR-374a mimic or inhibitor. miR-374a mimic reduced MCP-1 mRNA expression and migration of co-cultured U937 cells, whereas miR-374a inhibition had the opposite effects. Additionally, interleukin-6 and -18 and tumor necrosis factor-α levels were downregulated by transfection of miR-374a mimic. On the other hand, MCP-1 overexpression reversed the inhibitory effects of miR-374a in HK2 cells. Thus, miR-374a suppresses the inflammatory response in DN through negative regulation of MCP-1 expression. These findings suggest that therapeutic strategies that target the miR-374a/MCP-1 axis can be an effective treatment for DN.

SUBMITTER: Yang Z

PROVIDER: S-EPMC6095963 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease.

Project description:MicroRNAs are critical regulators of gene expression controlling cellular processes including inflammation. We explored their role in the pathogenesis of inflammatory bowel disease (IBD) and identified reduced expression of miR-374a-5p in IBD monocytes that correlated with a module of up-regulated genes related to the inflammatory response. Key proinflammatory module genes, including for example TNFα, IL1A, IL6, and OSM, were inversely correlated with miR-374a-5p and were validated in vitro. In colonic biopsies, miR-374a-5p was again reduced in expression and inversely correlated with the same inflammatory module, and its levels predicted subsequent response to anti-TNF therapy. Increased miR-374a-5p expression was shown to control macrophage-driven inflammation by suppressing proinflammatory mediators and to reduce the capacity of monocytes to migrate and activate T cells. Our findings suggest that miR-374a-5p reduction is a central driver of inflammation in IBD, and its therapeutic supplementation could reduce monocyte-driven inflammation in IBD or other immune-mediated diseases.

| S-EPMC8980842 | biostudies-literature

miR-23a-3p regulates the inflammatory response and fibrosis in diabetic kidney disease by targeting early growth response 1.

Project description:Diabetic kidney disease (DKD) has become the most common cause of chronic kidney disease. Proteinuria is generally considered one of the clinical indicators of renal damage, and it is also closely related to the progression of DKD. Accumulating evidence indicates that proteinuria induces an upregulation of the expression levels of inflammatory cytokines and fibrosis markers in renal tubular epithelial cells, but the mechanism remains unclear. Previously, we showed that early growth response 1 (Egr1) played a key role in renal tubular injury. However, the upstream mechanism of Egr1 in the development of DKD is poorly understood. In this study, we found that albumin stimulation significantly increased the expression levels of Egr1, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and fibronectin (FN) in HK-2 cells but decreased miR-23a-3p levels. We then identified that miR-23a-3p targeted the 3' untranslated region (UTR) of Egr1 and directly suppressed the expression of Egr1. Moreover, we found that overexpression and inhibition of miR-23a-3p in HK-2 cells attenuated and promoted the expression of IL-6, TNF-α, and FN, respectively. Additionally, Egr1 silencing reversed the inflammation and fibrosis caused by the miR-23a-3p inhibitor. Thus, we conclude that miR-23a-3p attenuates the development of DKD through Egr1, suggesting that targeting miR-23a-3p may be a novel therapeutic approach for DKD.

| S-EPMC8585819 | biostudies-literature

miR-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting TSPAN8.

Project description:BackgroundDiabetic nephropathy (DN) is one of the most common and serious complications of diabetes, which can lead to renal failure and fatality. miRNAs are an important class of endogenous non-coding RNAs implicated in a wide range of biological processes and pathological conditions. This study aims to investigate the potential functional roles of miR-543 in DN and its underlying mechanisms.MethodsqRT-PCR was performed to detect the expression levels of miR-543 and TSPAN8 in kidney tissues of mice with DN. Western blot (WB) was used to measure the protein levels. CCK8 assay was employed to evaluate the proliferation of HK2 cells. Dual luciferase reporter assay was conducted to verify the functional interaction between miR-543 and TSpan8.ResultsThe downregulation of miR-543 and upregulation of TSPAN8 were observed in kidney tissues of mice with DN. miR-543 mimic significantly decreased cell proliferation and autophagy in high-glucose (HG)-induced HK2 cells, and promoted cell fibrosis. We further identified a putative binding site between miR-543 and TSPAN8, which was validated by Dual luciferase reporter assay. The treatment of miR-543 mimic and miR-543 inhibitor could reduce or increase TSPAN8 protein level respectively. We further showed that the overexpression of TSPAN8 could attenuate HG-induced cell injury by reducing fibrosis and increase autophagy. The effects of miR-543 mimic in proliferation, fibrosis, and autophagy were rescued by TSPAN8 overexpression.ConclusionsOur study indicate that miR-543 mediates high-glucose induced DN via targeting TSPAN8. Interfering miR-543/TSPAN8 axis could serve as potential approach to ameliorate DN.

| S-EPMC8895563 | biostudies-literature

miR-27a regulates inflammatory response of macrophages by targeting IL-10.

Project description:Although microRNAs were shown to participate in innate immune responses, it is not completely understood how they regulate negative immunomodulatory events. IL-10 is an important anti-inflammatory mediator that prevents excessive inflammation and associated immunological pathologies. Although the regulation of IL-10 expression has been well studied at both the transcriptional and translational levels, it is less clear how microRNAs control IL-10 expression during inflammation. In this study, we found that miR-27a is downregulated in macrophages following stimulation through TLR2 and TLR4, but not TLR3. Upregulation of miR-27a enhanced the expression of proinflammatory cytokines in TLR2/4-activated macrophages. Conversely, knockdown of miR-27a diminished cytokine expression. Mechanistically, we found that miR-27a negatively regulates IL-10 expression; upregulation of miR-27a decreases, whereas downregulation of miR-27a increases, IL-10 expression in activated macrophages. Likely due to the decreased expression of IL-10, upregulation of miR-27a diminished IL-10-dependent STAT3 phosphorylation in TLR4-activated macrophages. Consistent with IL-10 being a potential mediator for the role of miR-27a in the immune response, blocking IL-10 abolished the enhancing effect of miR-27a on TLR4-activated inflammation. In conclusion, our study identified miR-27a downregulation as a negative-regulatory mechanism that prevents overly exuberant TLR2- and TLR4-driven inflammatory responses.

| S-EPMC4065847 | biostudies-literature

miR-93 regulates Msk2-mediated chromatin remodelling in diabetic nephropathy.

Project description:How the kidney responds to the metabolic cues from the environment remains a central question in kidney research. This question is particularly relevant to the pathogenesis of diabetic nephropathy (DN) in which evidence suggests that metabolic events in podocytes regulate chromatin structure. Here, we show that miR-93 is a critical metabolic/epigenetic switch in the diabetic milieu linking the metabolic state to chromatin remodelling. Mice with inducible overexpression of a miR-93 transgene exclusively in podocytes exhibit significant improvements in key features of DN. We identify miR-93 as a regulator of nucleosomal dynamics in podocytes. miR-93 has a critical role in chromatin reorganization and progression of DN by modulating its target Msk2, a histone kinase, and its substrate H3S10. These findings implicate a central role for miR-93 in high glucose-induced chromatin remodelling in the kidney, and provide evidence for a previously unrecognized role for Msk2 as a target for DN therapy.

| S-EPMC4931323 | biostudies-literature

MiR-374a suppresses lung adenocarcinoma cell proliferation and invasion by targeting TGFA gene expression.

Project description:Aberrant expression of miR-374a has been reported in several types of human cancers, including lung cancer. However, the functional significance and molecular mechanisms underlying the role of miR-374a in lung cancer remain largely unknown. We found that the expression of miR-374a was significantly downregulated in lung adenocarcinoma tissues compared to adjacent normal lung tissues in samples included in The Cancer Genome Atlas. Functional studies revealed that overexpression of miR-374a led to inhibition of lung adenocarcinoma cell proliferation, migration and invasion and that miR-374a negatively regulated transforming growth factor-alpha (TGFA) gene expression by directly targeting the 3'-UTR of TGFA mRNA. Treating lung adenocarcinoma cells with TGF-α neutralizing antibody resulted in suppression of cell proliferation and invasion, which mimicked the action of miR-374a. Additionally, TGFA gene expression was significantly higher in tumor tissues compared to adjacent normal tissue and high TGFA gene expression strongly correlated with poor survival in patients with lung adenocarcinoma. Taken together, our studies suggest that miR-374a suppresses lung adenocarcinoma cell proliferation and invasion via targeting TGFA gene expression. Our findings may provide novel treatment strategies for lung adenocarcinoma patients.

| S-EPMC4876989 | biostudies-literature

Rack1 regulates pro-inflammatory cytokines by NF-κB in diabetic nephropathy.

Project description:Diabetic nephropathy (DN) is one of the chronic microvascular diseases of diabetes. Studies revealed that inflammation is involved in the development of DN. However, its mechanisms are not fully clear. Here, we screened DN-related mRNAs by RNA sequencing in the renal tissues of db/db DN mice and normal control mice. The Swiss-Model, ZDOCK 3.0.2 and PyMOL 2.3.2 were applied for bioinformatics analysis. In total, we obtained 6,820 mRNAs that were dysexpressed in DN. Among them, Receptor for Activated C Kinase 1 (Rack1) was focused on for its high fold changes and high values of fragments per kilobase million (FPKM) in both two groups (FPKM >100). Moreover, Rack1 was highly expressed in DN in vivo and in vitro. Results displayed that the expressions of pro-inflammatory cytokines Mcp-1 and Tnf-α were increased when Rack1 was overexpressed in cells cultured with low glucose while the expressions of Mcp-1 and Tnf-α were decreased when Rack1 was silenced in cells cultured with high glucose. Furthermore, results showed that the established DN inflammatory factor nuclear factor NF-kappa-B (NF-κB) was regulated by Rack1 via the direct interaction between Rack1 and NF-κB subunits P50 and P65. In summary, this identified Rack1 could play an important role in the inflammation of DN via NF-κB, which can provide new insight for DN research.

| S-EPMC9137783 | biostudies-literature

Inflammatory Targets in Diabetic Nephropathy.

Project description:One of the most frequent complications in patients with diabetes mellitus is diabetic nephropathy (DN). At present, it constitutes the first cause of end stage renal disease, and the main cause of cardiovascular morbidity and mortality in these patients. Therefore, it is clear that new strategies are required to delay the development and the progression of this pathology. This new approach should look beyond the control of traditional risk factors such as hyperglycemia and hypertension. Currently, inflammation has been recognized as one of the underlying processes involved in the development and progression of kidney disease in the diabetic population. Understanding the cascade of signals and mechanisms that trigger this maladaptive immune response, which eventually leads to the development of DN, is crucial. This knowledge will allow the identification of new targets and facilitate the design of innovative therapeutic strategies. In this review, we focus on the pathogenesis of proinflammatory molecules and mechanisms related to the development and progression of DN, and discuss the potential utility of new strategies based on agents that target inflammation.

| S-EPMC7074396 | biostudies-literature

Chlorotoxin fusion protein regulates miR-374a and TNFAIP8 expression and inhibits glioma cell proliferation and promotes apoptosis.

Project description:Glioblastoma multiforme is the most common primary central nervous system malignancy, accounting for half of all intracranial primary tumors. In this study we constructed a multifunctional chlorotoxin fusion protein E-CHP that combines enhanced green fluorescent protein (E), glioma-targeting peptide chlorotoxin (C), destabilizing lipid membrane peptide riHA2 (H), and C-terminal and mouse double minute domains of p53 (P). E-CHP was expressed in Escherichia coli and purified by His affinity chromatography. Fluorescence microscopy observation showed that E-CHP could effectively target glioma cells; real-time quantitative PCR revealed that E-CHP increased miR-374a expression; and the dual luciferase reporter assay showed that tumor necrosis factor alpha-induced protein (TNFAIP)8 is a direct target of miR-374a. E-CHP and miR-374a inhibited the proliferation and migration of glioma cells, and Western blot analysis indicated that they suppressed TNFAIP8 expression in glioma cells and promoted the expression of caspase-3 and -8. Finally, E-CHP and miR-374a stimulated the apoptosis of glioma cells, as determined by flow cytometry analysis. These results suggest that miR-374a is a new candidate target for glioma therapy, whereas E-CHP fusion protein has the potential to be developed as a multifunctional carrier for targeted drug delivery and therapy.

| S-EPMC7547943 | biostudies-literature

Long non-coding RNA MEG3 promotes fibrosis and inflammatory response in diabetic nephropathy via miR-181a/Egr-1/TLR4 axis.

Project description:Long non-coding RNAs (lncRNAs) play vital roles in diabetic nephropathy (DN). This research aimed to study the potential role and underlying molecular mechanisms of long non-coding RNA MEG3 in DN. We found that MEG3 was upregulated in DN in vivo and in vitro and could enhance cell fibrosis and inflammatory response in DN. MEG3 functioned as an endogenous sponge for miR-181a in mesangial cells (MCs) via direct targeting and in an Ago2-dependent manner. MiR-181a inhibition promoted MC fibrosis and inflammatory response. In addition, Egr-1 was confirmed as a target gene of miR-181a. Further investigations verified that MEG3 promotes fibrosis and inflammatory response via the miR-181a/Egr-1/TLR4 axis in vitro and in vivo. These results provide new insights into the regulation between MEG3 and the miR-181a/Egr-1/TLR4 signaling pathway during DN progression.

| S-EPMC6594792 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data