MiR-30a-5p ameliorates LPS-induced inflammatory injury in human A549 cells and mice via targeting RUNX2

Li, Pibao; Yao, Yanfen; Ma, Yuezhen; Chen, Yanbin

doi:10.1177/1753425920971347

Cited by 11 publications

(10 citation statements)

References 21 publications

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“…In addition, microRNA (miR)-297, miR-150 and miR-216a are expressed at low levels in ARDS. These miRs exert protective effects against LPS-induced injury in A549 cells by reducing inflammatory cytokine secretion (17,23,24). The present study reported an excessive production of TNF-α, IL-6 and IL-1β in LPS-treated A549 cells, which was consistent with the findings reported previously.…”

Section: Discussionsupporting

confidence: 93%

LPS‑induced inflammatory response and apoptosis are mediated by Fra‑1 upregulation and binding to YKL‑40 in A549 cells

Wang

Liu

et al. 2021

Exp Ther Med

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Acute respiratory distress syndrome (ARDS) is a multifactorial syndrome that leads to increased morbidity and mortality in infants and children. The identification of novel biomarkers is critical for the treatment of ARDS. The present study aimed to investigate the effects of chitinase-3-like-1 protein (CHI3L1 or YKL-40) in an in vitro model of ARDS and to explore the potential underlying mechanisms. The in vitro model of ARDS was established in A549 alveolar epithelial type II cells, which were treated by lipopolysaccharide (LPS) to induce inflammation. Transfection was performed to alter YKL-40 expression. The mRNA and protein expression of YKL-40 was determined using reverse transcription-quantitative PCR and western blotting, respectively. Cell Counting Kit-8 and TUNEL assays were used to evaluate the cell viability and apoptosis, respectively. The production of cytokines was evaluated using specific ELISA kits. The relationship between YKL-40 and Fos-related antigen 1 (Fra-1) was verified using luciferase reporter and chromatin immunoprecipitation assays. The expression of the apoptotic proteins was detected using western blotting. The expression levels of YKL-40 and Fra-1 were increased in LPS-treated A549 cells. Higher levels of pro-inflammatory cytokines and induction of cell apoptosis were observed in LPS-treated A549 cells compared with the control. YKL-40 knockdown in LPS-treated A549 cells significantly decreased the production of pro-inflammatory cytokines and reduced cell apoptosis, whereas it concomitantly caused upregulation of Bax and downregulation of Bcl-2, cleaved caspase-3 and cleaved caspase-9. In addition, Fra-1 could directly bind to YKL-40 promoter and regulate its expression level. Overexpression of YKL-40 partly decreased the inhibitory effects of Fra-1 knockdown on the inflammatory response and induction of apoptosis. In summary, the findings from the present study indicated that Fra-1 could bind to YKL-40 and regulate its expression, whereas YKL-40 knockdown could further suppress LPS-induced inflammatory response and apoptosis in A549 cells. These data may provide novel evidence on the diagnosis and therapy of ARDS.

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Section: Discussionsupporting

confidence: 93%

LPS‑induced inflammatory response and apoptosis are mediated by Fra‑1 upregulation and binding to YKL‑40 in A549 cells

Wang

Liu

et al. 2021

Exp Ther Med

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“…The data showed that miR-30a-5p mimics effectively restrained excessive autophagy induced by MYOCD knockdown and restored the expression of contractile proteins. It has been reported that miR-30a-5p could inhibit the activation of nuclear factor κB (NF-κB) in many types of cells [ 23 – 25 ]. NF-κB activation has also been shown to inhibit myocardin expression and myocardin-mediated smooth muscle contractile marker genes [ 26 – 29 ].…”

Section: Discussionmentioning

confidence: 99%

Myocardin/microRNA-30a/Beclin1 signaling controls the phenotypic modulation of vascular smooth muscle cells by regulating autophagy

et al. 2022

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Upon vascular injury, vascular smooth muscle cells (VSMCs) change from a contractile phenotype to a synthetic phenotype, thereby leading to atherogenesis and arterial restenosis. Myocardin (MYOCD) is essential for maintaining the contractile phenotype of VSMCs. Deletion of MYOCD in VSMCs triggers autophagy. However, the molecular mechanism underlying the effect of MYOCD on autophagy is not clear. In this study, knockdown of MYOCD in human aortic VSMCs (HA-VSMCs) triggered autophagy and diminished the expression of SMC contractile proteins. Inhibition of autophagy in MYOCD-knockdown cells restored the expression of contractile proteins. MYOCD activated the transcription of miR-30a by binding to the CArG box present in its promoter, as confirmed by luciferase reporter and chromatin immune coprecipitation assays, while miR-30a decreased the expression of autophagy protein-6 (ATG6, also known as beclin1) by targeting its 3′UTR. Restoring the expression of miR-30a in MYOCD-knockdown cells upregulated the levels of contractile proteins. Treatment of VSMCs with platelet-derived growth factor type BB (PDGF-BB) resulted in the transformation of VSMCs to a proliferative phenotype. A low level of miR-30a was observed in PDGF-BB-treated HA-VSMCs, and re-expression of miR-30a led to a decrease in proliferative marker expression. Furthermore, using a wire injury mouse model, we found that miR-30a expression was significantly downregulated in the arterial tissues of mice and that restoration of miR-30a expression at the injured site abolished neointimal formation. Herein, MYOCD could inhibit autophagy by activating the transcription of miR-30a and that miR-30a-mediated autophagy defects could inhibit intimal hyperplasia in a carotid arterial injury model.

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“…According to Li et al, miR-30a-5p inhibits phosphorylation levels of STAT3, JNK, p56 and IκBα. Also, miR-30a-5p ameliorates LPS-induced inflammatory injury in human A549 cells and mice via targeting Runt-related transcription factor 2 (RUNX2) [21].…”

Section: Discussionmentioning

confidence: 99%

miR-30a-5p Augments the Anti-inflammatory Effects of Dexmedetomidine in LPS-induced BV2 Cells

Kim

Yang

2022

Korean J Clin Lab Sci

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Neuroinflammation is defined as a neurological inflammation within the brain and the spinal cord. In neuroinflammation, microglia are the tissue-resident macrophages of the central nervous system, which act as the first line of defense against harmful pathogens. Dexmedetomidine (Dex) has an anti-inflammatory effect in many neurological conditions. Additionally, the microRNA-30a-5p (miR-30a-5p) mimic has been proven to be effective in macrophages in inflammatory conditions. This study aimed to investigate the synergistic anti-inflammatory effects of both miR-30a-5p and Dex in lipopolysaccharide (LPS)-induced BV2 cells. This study showed that miR-30a-5p and Dex decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation in LPS-induced BV2 cells. MiR-30a-5p and Dex alleviated tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), LPS-induced phosphorylation c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK) and p38. Also, the expression of the NOD-like receptor pyrin domain containing 3 inflammasome (NLRP3), cleaved caspase-1, and ASC was inhibited. Furthermore, LPS-stimulated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression were attenuated by Dex and miR-30a-5p. Our results indicate that a combination of Dex and miR-30a-5p, attenuates NF-κB activation, the mitogen-activated protein kinase (MAPK) signaling pathway, and inflammatory mediators involved in LPS-induced inflammation and inhibits the activation of the NLRP3 inflammasome in LPS-activated BV2 cells.

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MiR-30a-5p ameliorates LPS-induced inflammatory injury in human A549 cells and mice via targeting RUNX2

Cited by 11 publications

References 21 publications

LPS‑induced inflammatory response and apoptosis are mediated by Fra‑1 upregulation and binding to YKL‑40 in A549 cells

LPS‑induced inflammatory response and apoptosis are mediated by Fra‑1 upregulation and binding to YKL‑40 in A549 cells

Myocardin/microRNA-30a/Beclin1 signaling controls the phenotypic modulation of vascular smooth muscle cells by regulating autophagy

miR-30a-5p Augments the Anti-inflammatory Effects of Dexmedetomidine in LPS-induced BV2 Cells

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