RETRACTED ARTICLE: Restoring microRNA-499-5p Protects Sepsis-Induced Lung Injury Mice Via Targeting Sox6

Abstract

Background MicroRNAs (miRs) are known to participate in sepsis; hence, we aim to discuss the protective effect of miR-499-5p targeting sex-determining region Y-related high-mobility-group box 6 (Sox6) on sepsis-induced lung injury in mice. Methods The sepsis-induced lung injury model was established by cecal ligation and puncture. The wet/dry weight (W/D) ratio, miR-499-5p, Sox6, Caspase-3 and Caspase-9 expression in lung tissues of mice were tested. Lung injury score, collagen fibers and the degree of pulmonary fibrosis in lung tissues were determined. Further, the cell apoptosis in lung tissues was measured. The inflammatory factors contents and oxidative stress indices in bronchoalveolar lavage fluid (BALF) and lung tissues were detected via loss- and gain-of-function assays. The targeting relation between miR-499-5p and Sox6 was verified. Results W/D ratio and Sox6 were increased while miR-499-5p was decreased in lung tissues of sepsis-induced lung injury mice. Restored miR-499-5p or depleted Sox6 alleviated lung tissues pathology, reduced lung injury score, collagen fibers, the degree of pulmonary fibrosis, TUNEL positive cells, Caspase-3 and Caspase-9 protein expression and inflammatory factors contents in BALF and lung tissues as well as oxidative stress response in lung tissues of sepsis-induced lung injury mice. miR-499-5p targeted Sox6. Conclusion High expression of miR-499-5p can attenuate cell apoptosis in lung tissues and inhibit inflammation of sepsis-induced lung injury mice via depleting Sox6, and it is a potential candidate marker and therapeutic target for sepsis-induced lung injury.

miR-155: A Potential Biomarker for Predicting Mortality in COVID-19 Patients

“…We studied the expressions of five miRNAs (miR-21, -146a, -146b, -155 and -499) in our cohort and found that miRs-146a, -146b, -21 and -499 showed an upward trend in the levels of expression in the sick participants (the results for miR146b are significant). These results are in accordance with the notion that these miRNAs play a role in fighting inflammation or protecting against the damage caused by inflammation [9][10][11][12][13].…”

“…Given the potential of miRNAs as clinical biomarkers, we analyzed the levels of five miRNAs associated with inflammation and acute lung injury (ALI), key features of COVID-19 [7]. These miRNAs have been shown to regulate the expression of genes related to inflammation: miR-155 has been shown to target SHIP1 and SOCS, two negative regu-lators of the macrophage inflammatory response [8]; the miR-146 family targets include IRAK1 and TRAF6, involved in regulation of cytokine-responsive gene expression, and the proinflammatory cytokines IL-6, and IL-8 [9]; miR-21 modulates the cytokine IL-12 [10]; and miR-499 targets SOX6, which has been connected to sepsis-induced lung injury [11]. miRNAs analysis was performed on blood samples obtained from COVID-19 patients and healthy participants, upon admission to the hospital, aiming to explore their potential as predictors of mortality.…”

Expression of MicroRNAs in Sepsis-Related Organ Dysfunction: A Systematic Review

“…Specifically, in this study, the overexpression of miR-125-5p allowed reduced levels of pulmonary oedema, inflammation, and apoptosis in rats with induced ALI [ 217 ]. Even miR-499-5p showed similar functions in the work of Zhang et al, but via targeting and degrading Sox6 [ 218 ].…”

Combination of azithromycin and methylprednisolone alleviates Mycoplasma pneumoniae induced pneumonia by regulating miR‑499a‑5p/STAT3 axis

“…Existing studies have revealed a downregulated expression of miR-499a-5p in clinical patients suffering from hepatitis B virus or autism, and in in vivo models including gliomas, lung adenocarcinoma and myocardial injury (11)(12)(13)(14)(15). In particular, miR-499a-5p was declined in sepsis-induced lung injury, and restoration of miR-499-5p protected the lung from injury by inhibiting inflammation (16). Therefore, the involvement of miR-499a-5p in inflammation-and infection-related diseases was hypothesized (15,17).…”