MicroRNA-140-5p ameliorates the high glucose-induced apoptosis and inflammation through suppressing TLR4/NF-κB signaling pathway in human renal tubular epithelial cells

Su, Jie; Ren, Jian; Chen, Haiyan; Liu, Bo

doi:10.1042/bsr20192384

Cited by 38 publications

(19 citation statements)

References 48 publications

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“…In our previous study, we found that miR-140-5p could alleviate cisplatin-induced oxidative stress by regulating the Nrf2/ARE signaling pathway (Liao et al, 2017). Additionally, in diabetic nephropathy, the expression of miR-140-5p in kidney tissues was significantly down-regulated, and miR-140-5p protected HK-2 cells from high glucose-induced injury by inhibiting the TLR4/NF-kappaB pathway (Su et al, 2020). Several studies suggested that miR-140-5p may be linked to fibrosis in some diseases.…”

Section: Introductionmentioning

confidence: 95%

MicroRNA-140-5p Mediates Renal Fibrosis Through TGF-β1/Smad Signaling Pathway by Directly Targeting TGFBR1

et al. 2020

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Renal tubulointerstitial fibrosis is usually the final outcome of various end-stage renal diseases. Recent studies have reported that microRNAs (miRNAs) play an important role in renal fibrosis. However, the biological function of microRNAs in renal fibrosis is complicated and remains unclear. In this study, our results show that miR-140-5p expression is significantly down-regulated in mice with unilateral ureteral obstruction and human proximal tubule epithelial cells (HK2) treated with TGF-β1. The knockdown of miR-140-5p upregulates the expression levels of collagen I, collagen IV, and α-SMA, decreases E-cadherin expression, and increases Smad-2/3 phosphorylation. In contrast, the overexpression of miR-140-5p decreases the expression levels of collagen I, collagen IV, and α-SMA, enhances E-cadherin expression, and inhibits the phosphorylation of Smad-2/3 in HK2 cells treated with TGF-β1. The dual-luciferase reporter assay revealed that TGFBR1 is a direct target gene of miR-140-5p. The enforced expression of miR-140-5p significantly inhibited the expression of TGFBR1 in HK2 cells. Furthermore, the knockdown of TGFBR1 has a similar effect of miR-140-5p overexpression on blocking the TGF-β1/smad signal pathway activation. In contrast, the overexpression of TGFBR1 reverses the effect of miR-140-5p inhibition on the activation of the TGF-β1/smad signal pathway. This study demonstrates that miR-140-5p regulates the TGF-β1/smad signaling pathway by suppressing the expression of TGFBR1. Therefore, miR-140-5p may have a therapeutic potential for preventing fibrotic kidney diseases through inhibiting the TGF-β1/Smad signaling pathway by directly targeting TGFBR1.

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Section: Introductionmentioning

confidence: 95%

MicroRNA-140-5p Mediates Renal Fibrosis Through TGF-β1/Smad Signaling Pathway by Directly Targeting TGFBR1

et al. 2020

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“…Diabetic nephropathy-related OxS is also improved upon elevation of miR-214 via using uncoupling protein 2 (UCP2) so as to affect signaling via ROS/AKT/mTOR pathway [274]. miR-140-5p also ameliorated HG-promoted ROS generation, inflammation, and apoptosis in human renal tubular epithelial cells (HK-2) via repressing signaling via TLR4/NF-κB [275]. ROS production along with apoptosis of HK-2 became potentiated upon HG-triggered upregulation of miR-125b, which directly targets a protective molecule, angiotensin-converting enzyme 2 (ACE2) [276].…”

Section: Mirnas In Mets-a Link With Obesity and Insulin Resistance/hymentioning

confidence: 99%

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Włodarski

Strycharz

Wróblewski

et al. 2020

IJMS

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Oxidative stress (OxS) is the cause and the consequence of metabolic syndrome (MetS), the incidence and economic burden of which is increasing each year. OxS triggers the dysregulation of signaling pathways associated with metabolism and epigenetics, including microRNAs, which are biomarkers of metabolic disorders. In this review, we aimed to summarize the current knowledge regarding the interplay between microRNAs and OxS in MetS and its components. We searched PubMed and Google Scholar to summarize the most relevant studies. Collected data suggested that different sources of OxS (e.g., hyperglycemia, insulin resistance (IR), hyperlipidemia, obesity, proinflammatory cytokines) change the expression of numerous microRNAs in organs involved in the regulation of glucose and lipid metabolism and endothelium. Dysregulated microRNAs either directly or indirectly affect the expression and/or activity of molecules of antioxidative signaling pathways (SIRT1, FOXOs, Keap1/Nrf2) along with effector enzymes (e.g., GPx-1, SOD1/2, HO-1), ROS producers (e.g., NOX4/5), as well as genes of numerous signaling pathways connected with inflammation, insulin sensitivity, and lipid metabolism, thus promoting the progression of metabolic imbalance. MicroRNAs appear to be important epigenetic modifiers in managing the delicate redox balance, mediating either pro- or antioxidant biological impacts. Summarizing, microRNAs may be promising therapeutic targets in ameliorating the repercussions of OxS in MetS.

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“…Chen et al analyzed 9 differentially expressed miRNAs in the renal tubular epithelial cell population of mice with fatal ischemia-induced acute kidney injury, in which miR-483 was significantly downregulated [30]. More importantly, Su et al analyzed miRNA expression profiles in kidney tissue of DN patients through miRNA microarray, and miR-483-5p was downregulated in the miRNAs [15]. Therefore, in this study, we first analyzed the expression levels of miR-483-5p in serums of different subjects and confirmed that miR-483-5p was significantly decreased in the serums of DN patients.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have analyzed the differentially expressed miRNAs in peripheral blood of DN patients and healthy controls including miR-483-5p [15]. miR-483 is located on chromosome 11p15.5, and its level imbalance is involved in a variety of human diseases, including breast cancer, nasopharyngeal carcinoma, myocardial infarction, and systemic sclerosis [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

miRNA-483–5p Targets HDCA4 to Regulate Renal Tubular Damage in Diabetic Nephropathy

et al. 2021

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This study was designed to evaluate the diagnostic value of miR-483–5p in diabetic nephropathy (DN), and its effect and mechanism on apoptosis and inflammation of human proximal renal tubular cells (HK2) induced by high glucose (HG). Thirty healthy controls, 30 types 2 diabetes mellitus (T2DM) patients, and 28 DN patients were enrolled. miR-483–5p mRNA levels in serum were analyzed by RT-qPCR assays. The receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of miR-483–5p in DN. HK2 cells were induced by HG to establish an in vitro study model. CCK-8 and flow cytometry was used to detect cell viability, apoptosis, and reactive oxygen species (ROS) generation. Inflammation levels were measured by ELISA. Luciferase reporter assay was used to detect target genes of miR-483–5p. miR-483–5p was decreased in DN patients. The decreased level of miR-483–5p was positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with proteinuria. miR-483–5p can significantly distinguish DN patients from healthy controls and T2DM and has a high diagnostic value. miR-483–5p decreased in HK2 cells induced by HG, and overexpression of miR-483–5p reversed HG-induced decreased cell activity, increased apoptosis, ROS production, and inflammation. Histone deacetylase 4 (HDCA4) was markedly increased in DN patients and HG-induced HK2 cells. miR-483–5p directly targeted HDCA4, and increasing miR-483–5p inhibited HDCA4 increased in HG-induced HK2. In conclusion, the results indicate that reduction of miR-483–5p has a high diagnostic value in DN, and overexpression of miR-483–5p has a certain protective effect on HK2 cells induced by HG by targeting HDCA4.

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MicroRNA-140-5p ameliorates the high glucose-induced apoptosis and inflammation through suppressing TLR4/NF-κB signaling pathway in human renal tubular epithelial cells

Cited by 38 publications

References 48 publications

MicroRNA-140-5p Mediates Renal Fibrosis Through TGF-β1/Smad Signaling Pathway by Directly Targeting TGFBR1

MicroRNA-140-5p Mediates Renal Fibrosis Through TGF-β1/Smad Signaling Pathway by Directly Targeting TGFBR1

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

miRNA-483–5p Targets HDCA4 to Regulate Renal Tubular Damage in Diabetic Nephropathy

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