miR‑34a increases inflammation and oxidative stress levels in patients with necrotizing enterocolitis by downregulating SIRT1 expression

Abstract

The mir-34a/SirT1 signaling axis is an important signaling axis in tumors and diseases. notably, low SirT1 expression in the intestinal tissues of patients with necrotizing enterocolitis (nec) has been reported. However, whether mir-34a/SirT1 signaling as a target to protect the intestines during the nec process is unclear and remains to be elucidated. Blood samples were collected from 30 patients with nec, and an nec rat model was used. The mir-34a and SirT1 gene and protein expression levels were assayed by qPcr and Western blotting method. The inflammatory cytokine levels and oxidative stress levels were detected using the eliSa method. The results demonstrated that birth weight, albumin and glucose concentrations were significantly decreased in the NEC patient group compared with the control group, but the c-reactive protein (crP) and procalcitonin (PcT) concentrations were significantly increased. The mir-34a expression level was notably increased in the nec group, but the SirT1 expression level was markedly decreased. Notably, the miR-34a was significantly correlated with NEC severity and the concentrations of crP, PcT, il-6, TnF-α, il-1β, il-8, McP-1, VcaM1 and malondialdehyde (MDA), but was significantly negatively correlated with SirT1 gene expression and the concentration of il-10. intestinal villi damage in nec rats was decreased with mir-34a inhibition and SirT1 activation treatment by decreasing the levels of inflammatory cytokines, including il-6, TnF-α, il-1β and il-8, and oxidative stress proteins, including McP-1, VcaM1, and Mda, as well as increasing the level of the anti-inflammatory cytokine IL-10. In addition, the results indicated that mir-34a inhibition and SirT1 activation strongly protected the intestine and decreased the damage caused by nec, not only by decreasing the protein levels of SirT1, , but also by increasing the il-10 protein levels. The mir-34a inhibition and SirT1 activation may decrease the damage caused by nec by decreasing proinflammatory cytokines and oxidative stress proteins and by increasing the anti-inflammatory cytokine pathway. Based on the aforementioned analysis, the mir-34a and SirT1 proteins may be potential novel therapeutic targets in nec.

Functional role of miR-34a in diabetes and frailty

“…The prolonged exposure of saturated fatty acids to MIN6 β-cells and pancreatic islets increased the expression of miR-34a ( Lovis et al, 2008 ). Furthermore, miR-34a leads to endothelial dysfunction and vascular senescence in diabetes ( Li et al, 2016 ; Carracedo et al, 2019 ; Thounaojam and Bartoli, 2019 ), increasing the overall risk of oxidative stress and inflammation with or without diabetes ( Li et al, 2016 ; Cheleschi et al, 2019 ; Xiong et al, 2019 ; Zimta et al, 2019 ; Li et al, 2021 ; Mahjabeen et al, 2021 ; Zhu et al, 2021 ).…”

The role and mechanisms of miRNA in neonatal necrotizing enterocolitis

“…Zhu et al . found that miR-34a was notably upregulated in NEC, which could promote the production of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8) and anti-inflammatory cytokines IL-10 by downregulating sirtuin1 (SIRT1) expression ( 39 ). Xia et al .…”

“…Zhu et al . found that intestinal villi injury can be ameliorated by miR-34a inhibitors and SIRT1 activators ( 39 ).…”

“…(37). Zhu et al found that miR-34a was notably upregulated in NEC, which could promote the production of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8) and anti-inflammatory cytokines IL-10 by downregulating sirtuin1 (SIRT1) expression (39). Xia et al indicated that C-kit expression was suppressed by TNF-α via miR-222 upregulation resulting in an increased inflammatory response (35).…”

“…Antagonists of miR-222 can reverse the decrease of c-kit expression (35). Zhu et al found that intestinal villi injury can be ameliorated by miR-34a inhibitors and SIRT1 activators (39).…”