MicroRNA let-7c-5p Suppressed Lipopolysaccharide-Induced Dental Pulp Inflammation by Inhibiting Dentin Matrix Protein-1-Mediated Nuclear Factor kappa B (NF-κB) Pathway In Vitro and In Vivo

Abstract

BackgroundLet-7c-5p is down-regulated in dental pulp tissues in inflammatory disorders. The microRNA (miR) molecule shows an anti-inflammation potential due to its direct regulation of dentin matrix protein-1 (DMP1), which promotes inflammation changes in dental pulp tissues. In the present study, the effect of let-7c-5p on lipopolysaccharide (LPS)-induced pulpitis was detected and the associated mechanism was explored.Material/MethodsDental pulp stem cells (DPSCs) were isolated from rat dental tissues, infected with let-7c-5p lentivirus particles, and subjected to LPS administration to induce inflammation. Then, the effect of let-7c-5p overexpression on LPS-induced impairments on DPSCs were detected and the mechanism was explained by focusing on the DMP1 expression and NF-κB pathway. The role of DMP1 in the anti-inflammation effect of let-7c-5p was assessed by incubating let-7c-5p-expressed DPSCs with DMP1 protein. The results of in vitro assays were verified in LPS-induced rat pulpitis models.ResultsLPS administration increased the production of IL-1β and TNF-α and decreased DPSCs viability by increasing the expression of DMP1 and activating NF-κB pathway. However, the induced expression of let-7c-5p relieved DPSCs from LPS-induced inflammation and suppressed DMP1 as well as NF-κB pathway. The incubation of let-7c-5p-expressed DPSCs with DMP1 protein blocked the effect of let-7c-5p. In in vivo experiments, the injection of let-7c-5p attenuated LPS-induced pulpitis by inhibiting DMP1-mediated NF-κB pathway.ConclusionsFindings outlined in the current study demonstrated the dental pulp protecting function of let-7c-5p during LPS-induced inflammation, which was exerted by inhibiting the DMP1-mediated NF-κB pathway.

Characterization of exosome-like vesicles derived from Cysticercus pisiformis and their immunoregulatory role in macrophages

“…Some of miRNAs could regulate innate immune response in inflammatory pathways through targeting signaling components. Previous studies suggested that let-7c-5p suppressed LPSinduced inflammation via targeting DMP1-mediated NF-κB pathway [50]. miR-9 was induced by LPS in human monocytes and neutrophils, and increased miR-9 acts as a feedback control of NF-κB dependent inflammatory response by inhibiting the expression of NFκB1 [51].…”

Characterization of exosome-like vesicles derived from Taenia pisiformis cysticercus and their immunoregulatory role on macrophages

“…Some of miRNAs could regulate innate immune response in in ammatory pathways through targeting signaling components. Previous studies suggested that let-7c-5p suppressed LPSinduced in ammation via targeting the DMP1-mediated NF-κB pathway [51]. miR-9 was induced by LPS in human monocytes and neutrophils, and increased miR-9 acts as a feedback control of the NF-κB dependent in ammatory response by inhibiting the expression of NFκB1 [52].…”

Prothrombotic effects of high uric acid in mice via activation of MEF2C-dependent NF-κB pathway by upregulating let-7c

“…On the contrary, certain studies indicated the inhibitory effect of let-7c on NF-κB as well. For example, let-7c attenuated the severity of pulpitis by inhibiting the NF-κB pathway in inflammatory disorders as NF-κB pathway increased the production of the inflammatory cytokines IL-1β and TNF-α and decreased stem cell viability [ 25 ]. Besides, let-7c was reported in other studies to inhibit and downregulate NF-κB phosphorylation [ 26 – 28 ].…”