MiR-21 Regulates TNF-α-Induced CD40 Expression via the SIRT1-NF-κB Pathway in Renal Inner Medullary Collecting Duct Cells

Abstract

Background/Aims: Recent studies have indicated that microRNA-21 (miR-21) is involved in the inflammatory response in relation to renal disease. Sirtuin1 (SIRT1) exerts renoprotective properties by counteracting inflammation. The activation of CD40 triggers inflammation that participates in renal inflammation and injury. The relationship between miR-21, SIRT1 and CD40, however, remains elusive. Methods: Immunohistochemistry, small-interfering RNA (siRNA) transfection, quantitative real-time PCR and western blotting were applied to assess the morphological, functional and molecular mechanisms in primary cultured renal inner medullary collecting duct (IMCD) cells. Results: TNF-α induced miR-21, CD40 and acetylated-NF-κBp65 (Ac-p65) expressions and reduced SIRT1 expression in IMCD cells. miR-21 mimics increased SIRT1 expression and attenuated Ac-p65 and CD40 expressions in TNF-α-induced IMCD cells, and the corresponding changes were observed with a miR-21 inhibitor. SIRT1 overexpression or activation by SRT1720 diminished TNF-α-induced CD40 and Ac-p65 expressions, which was reversed by SIRT1 siRNA or the inhibitors Ex527 and sirtinol and augmented by pretreatment with NF-κB siRNA. Further study found that the inhibitory effect of miR-21 on Ac-p65 and CD40 expressions was impeded by pretreatment with SIRT1 siRNA. Conclusion: The present study indicates that miR-21 inhibits TNF-α-induced CD40 expression in IMCD cells via the SIRT1-NF-κB signalling pathway, which provides new insight in understanding the anti-inflammatory effect of miR-21.

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

“…Moreover, miR-21-5p might protect monocyte from IHR-induced cell apoptosis and cytotoxicity by inhibiting TLR4/TNF-α/IL-6R-mediated inflammation. In line with our findings, previous studies have shown that miR-21 has anti-inflammatory and anti-apoptosis effects by inhibiting NF-κB-TNF-α-TLR and PDCD4-caspase-3 pathways, respectively, while TNF-α can suppress miR-21 functional axis [16][17][18]20,25,29,36]. The results open the possibility of using miR-21-5p mimic to overcome systemic inflammation and improve outcomes in OSA patients.…”

“…Certain miRNAs, including miR-21 and miR-23a, are induced by TLR signaling or negatively regulate TLR signaling [14]. Specifically, miR-21 is involved in anti-inflammatory response via inhibiting TLR, NF-κB, IL-6, and TNF-α signaling pathway, while high concentrations of TNF-α inhibit miR-21 functional axis [15][16][17][18][19][20]. In contrast, miR-23a may be involved in pro-inflammatory response via enhancing TNF-α and IL-6 secretions, while TLR signaling can inhibit miR-23a expression [21][22][23].…”

Endogenous Nampt upregulation is associated with diabetic nephropathy inflammatory‑fibrosis through the NF‑κB p65 and Sirt1 pathway; NMN alleviates diabetic nephropathy inflammatory‑fibrosis by inhibiting endogenous Nampt

“…Recent results have indicated that nuclear factor (NF)-κB signaling has a major role in innate immunity defense whereas sirtulin (SIRT)1 regulates the oxidative respiration and cellular survival ( 9 ). Additionally, NF-κB p65 signaling may stimulate glycolytic energy flux during acute inflammation, whereas SIRT1 activation inhibits NF-κB p65 signaling and enhances oxidative metabolism and reduces the expression of inflammatory and fibrotic factors, including tumor necrosis factor-α and transforming growth factor-β) ( 10 ). Previous findings have indicated that SIRT1 inhibits NF-κB p65 signaling directly by deacetylating the p65 subunit of NF-κB complex ( 10 ).…”

Underlying mechanism of the photodynamic activity of hematoporphyrin‑induced apoptosis in U87 glioma cells

“…The proteins associated with cell apoptosis were detected by apoptosis antibody array, and quantitative analysis revealed that TAP1 and NF-κB-mediated apoptosis signaling pathway was the most important pathway involved in PdT, with hematoporphyrin-induced apoptosis observed in glioma U87 cells. A recent study reported that miR-21 significantly contributes to the inflammatory response via the sirtuin 1-NF-κB signaling pathway (36). It implied that the miRNAs that specifically targeted TAP1 and NF-κB are important therapeutic targets (Fig.…”