MicroRNA-499-5p targets SIRT1 to aggravate lipopolysaccharide-induced acute lung injury

Yang, Fan; Yan, Jie; Lü, Yuan; Wang, Dengyun; Liu, Li; Wang, Zhengjun

doi:10.1080/10715762.2020.1863393

Cited by 11 publications

(6 citation statements)

References 55 publications

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“…34 EX527, an inhibitor of SIRT1, antagonized the protective effect of miR-499-5p on LPS-induced lung injury. 35 In this study, we also noted that EX527 aggravated oxidative stress in the intestines of NEC mice, with an increase in the activity of MDA and a decrease in the activity of GPx, which indirectly suggested an inhibitory effect of EX527 on oxidative stress injury. The intestinal mucosal barrier is of great significance for the maintenance of the intestinal barrier, which refers to the TJs between intestinal epithelial cells and other cells.…”

Section: Discussionsupporting

confidence: 63%

Protective Effect of the SIRT1-Mediated NF-κB Signaling Pathway against Necrotizing Enterocolitis in Neonatal Mice

et al. 2022

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Objective To discover the mechanism of the sirtuin 1 (SIRT1)-mediated nuclear factor-κB (NF-κB) pathway in the protection against necrotizing enterocolitis (NEC) in neonatal mice. Materials and Methods Neonatal mice were treated with EX527 (an inhibitor of SIRT1) and/or pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB). The survival rate of the mice was recorded. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the intestines. Furthermore, western blotting, enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction were conducted to measure the protein and gene expression, while corresponding kits were used to detect the levels of oxidative stress indicators. Results PDTC increased the survival rate of NEC mice. When compared with the NEC+ EX527 + PDTC group, the histological NEC score was higher in the NEC + EX527 group but lower in the NEC + PDTC group. SIRT1 expression in the intestines of NEC mice was downregulated, with an increase in p65 nuclear translocation. Additionally, malondialdehyde increased and glutathione peroxidase decreased in the intestines of NEC mice, with the upregulation of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α, as well as the downregulation of ZO-1, occludin, and claudin-4 in the intestines. However, the above changes could be improved by PDTC, which could be further reversed by EX527. Conclusion SIRT1 can mitigate inflammation and the oxidative stress response and improve intestinal permeability by mediating the NF-κB pathway, playing an important role in the alleviation of NEC.

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Section: Discussionsupporting

confidence: 63%

Protective Effect of the SIRT1-Mediated NF-κB Signaling Pathway against Necrotizing Enterocolitis in Neonatal Mice

et al. 2022

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“…This may explain, at least in part, why LNA-antimiR-34a treatment in the current study did not regulate several miR-34a targets genes known to contribute to cardiac protection including Bcl2, Pnuts, Sirt1, Vegfa and Vegfb. For example, of the upregulated miRNAs described in previous diabetic studies, a number including miR-195, miR-483-3p, miR-210, miR-451, miR-181c, miR-1183, miR-145, miR-199, miR-137 and miR-499 have been shown to regulate mRNAs that are recognized targets of miR-34a including Bcl2 and Sirt1 [27,[50][51][52][53][54][55][56][57][58] (Figure 7B). It is therefore probably not surprising that in a setting of diabetes in which multiple miRNAs are upregulated and targeting the same mRNAs, inhibiting miR-34a alone had no significant impact on the regulation of some target genes (Figure 7B).…”

Section: Discussionmentioning

confidence: 76%

In Vivo Inhibition of miR-34a Modestly Limits Cardiac Enlargement and Fibrosis in a Mouse Model with Established Type 1 Diabetes-Induced Cardiomyopathy, but Does Not Improve Diastolic Function

Bernardo

Yildiz

Kiriazis

et al. 2022

Cells

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MicroRNA 34a (miR-34a) is elevated in the heart in a setting of cardiac stress or pathology, and we previously reported that inhibition of miR-34a in vivo provided protection in a setting of pressure overload-induced pathological cardiac hypertrophy and dilated cardiomyopathy. Prior work had also shown that circulating or cardiac miR-34a was elevated in a setting of diabetes. However, the therapeutic potential of inhibiting miR-34a in vivo in the diabetic heart had not been assessed. In the current study, type 1 diabetes was induced in adult male mice with 5 daily injections of streptozotocin (STZ). At 8 weeks post-STZ, when mice had established type 1 diabetes and diastolic dysfunction, mice were administered locked nucleic acid (LNA)-antimiR-34a or saline-control with an eight-week follow-up. Cardiac function, cardiac morphology, cardiac fibrosis, capillary density and gene expression were assessed. Diabetic mice presented with high blood glucose, elevated liver and kidney weights, diastolic dysfunction, mild cardiac enlargement, cardiac fibrosis and reduced myocardial capillary density. miR-34a was elevated in the heart of diabetic mice in comparison to non-diabetic mice. Inhibition of miR-34a had no significant effect on diastolic function or atrial enlargement, but had a mild effect on preventing an elevation in cardiac enlargement, fibrosis and ventricular gene expression of B-type natriuretic peptide (BNP) and the anti-angiogenic miRNA (miR-92a). A miR-34a target, vinculin, was inversely correlated with miR-34a expression, but other miR-34a targets were unchanged. In summary, inhibition of miR-34a provided limited protection in a mouse model with established type 1 diabetes-induced cardiomyopathy and failed to improve diastolic function. Given diabetes represents a systemic disorder with numerous miRNAs dysregulated in the diabetic heart, as well as other organs, strategies targeting multiple miRNAs and/or earlier intervention is likely to be required.

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“… 638 , 639 Inflammation and oxidative stresses are essential for the progression of ALI. 640 However, the molecular mechanisms of sepsis-induced lung inflammatory injury are yet to be determined. SIRT1 has been widely reported to exert its anti-inflammatory function by regulating the production of proinflammatory cytokines.…”

Section: Introductionmentioning

confidence: 99%

The sirtuin family in health and disease

Zhang

Chen

et al. 2022

Sig Transduct Target Ther

292

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Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.

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MicroRNA-499-5p targets SIRT1 to aggravate lipopolysaccharide-induced acute lung injury

Cited by 11 publications

References 55 publications

Protective Effect of the SIRT1-Mediated NF-κB Signaling Pathway against Necrotizing Enterocolitis in Neonatal Mice

Protective Effect of the SIRT1-Mediated NF-κB Signaling Pathway against Necrotizing Enterocolitis in Neonatal Mice

In Vivo Inhibition of miR-34a Modestly Limits Cardiac Enlargement and Fibrosis in a Mouse Model with Established Type 1 Diabetes-Induced Cardiomyopathy, but Does Not Improve Diastolic Function

The sirtuin family in health and disease

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