Mmu-miR-27a-5p-Dependent Upregulation of MCPIP1 Inhibits the Inflammatory Response in LPS-Induced RAW264.7 Macrophage Cells

Cheng, Ying; Du, Lijun; Hu, Jiao; Zhu, Huapei; Xu, Kailian; Guo, Shiyu; Shi, Qi; Zhao, Tianjing; Pang, Feng; Jia, Xiaoyun; Wang, Fengyang

doi:10.1155/2015/607692

Cited by 26 publications

(16 citation statements)

References 25 publications

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“…In macrophages, miR-27a overexpression enhanced the expression of proinflammatory cytokines (IL-1β, IL-6, IL-12, and TNF-α), and diminished the expression of anti-inflammatory cytokine IL-10 ( 17 ). Also in macrophages, mmu-miR-27a was indicated as a proinflammatory gene, as its target gene MCPIP1 could decrease the secretion of IL-6, IL-1β, and IL-10, which were stimulated by LPS ( 15 ). These data indicated the complex and critical roles of miR-27a in inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

miR-27a protects human mitral valve interstitial cell from TNF-α-induced inflammatory injury via up-regulation of NELL-1

Chen

Zhang

et al. 2018

Braz J Med Biol Res

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MicroRNAs (miRNAs) have been reported to be associated with heart valve disease, which can be caused by inflammation. This study aimed to investigate the functional impacts of miR-27a on TNF-α-induced inflammatory injury in human mitral valve interstitial cells (hMVICs). hMVICs were subjected to 40 ng/mL TNF-α for 48 h, before which the expressions of miR-27a and NELL-1 in hMVICs were altered by stable transfection. Trypan blue staining, BrdU incorporation assay, flow cytometry detection, ELISA, and western blot assay were performed to detect cell proliferation, apoptosis, and the release of proinflammatory cytokines. We found that miR-27a was lowly expressed in response to TNF-α exposure in hMVICs. Overexpression of miR-27a rescued hMVICs from TNF-α-induced inflammatory injury, as cell viability and BrdU incorporation were increased, apoptotic cell rate was decreased, Bcl-2 was up-regulated, Bax and cleaved caspase-3/9 were down-regulated, and the release of IL-1β, IL-6, and MMP-9 were reduced. NELL-1 was positively regulated by miR-27a, and NELL-1 up-regulation exhibited protective functions during TNF-α-induced cell damage. Furthermore, miR-27a blocked JNK and Wnt/β-catenin signaling pathways, and the blockage was abolished when NELL-1 was silenced. This study demonstrated that miR-27a overexpression protected hMVICs from TNF-α-induced cell damage, which might be via up-regulation of NELL-1 and thus modulation of JNK and Wnt/β-catenin signaling pathways.

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Section: Discussionmentioning

confidence: 99%

miR-27a protects human mitral valve interstitial cell from TNF-α-induced inflammatory injury via up-regulation of NELL-1

Chen

Zhang

et al. 2018

Braz J Med Biol Res

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“…57 Influenza A virus (IAV) hijacks the miR-9/Regnase-1 axis, thereby benefitting the viral life cycle. 58 It has been reported that miR-139 and miR-27a-5P promote IL-6 expression by targeting Regnase-1 in human OA chondrocytes 59,60 (Figure 1b). In contrast, Regnase-1 acts as a broad suppressor of miRNA synthesis by counteracting Dicer, a central ribonuclease in miRNA processing.…”

Section: Functional Termination Of Regnase-1 Through Multiple Mechanismsmentioning

confidence: 97%

Regnase-1, a rapid response ribonuclease regulating inflammation and stress responses

et al. 2017

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RNA-binding proteins (RBPs) are central players in post-transcriptional regulation and immune homeostasis. The ribonuclease and RBP Regnase-1 exerts critical roles in both immune cells and non-immune cells. Its expression is rapidly induced under diverse conditions including microbial infections, treatment with inflammatory cytokines and chemical or mechanical stimulation. Regnase-1 activation is transient and is subject to negative feedback mechanisms including proteasome-mediated degradation or mucosa-associated lymphoid tissue 1 (MALT1) mediated cleavage. The major function of Regnase-1 is promoting mRNA decay via its ribonuclease activity by specifically targeting a subset of genes in different cell types. In monocytes, Regnase-1 downregulates IL-6 and IL-12B mRNAs, thus mitigating inflammation, whereas in T cells, it restricts T-cell activation by targeting c-Rel, Ox40 and Il-2 transcripts. In cancer cells, Regnase-1 promotes apoptosis by inhibiting anti-apoptotic genes including Bcl2L1, Bcl2A1, RelB and Bcl3. Together with up-frameshift protein-1 (UPF1), Regnase-1 specifically cleaves mRNAs that are active during translation by recognizing a stem-loop (SL) structure within the 3'UTRs of these genes in endoplasmic reticulum-bound ribosomes. Through this mechanism, Regnase-1 rapidly shapes mRNA profiles and associated protein expression, restricts inflammation and maintains immune homeostasis. Dysregulation of Regnase-1 has been described in a multitude of pathological states including autoimmune diseases, cancer and cardiovascular diseases. Here, we provide a comprehensive update on the function, regulation and molecular mechanisms of Regnase-1, and we propose that Regnase-1 may function as a master rapid response gene for cellular adaption triggered by microenvironmental changes.

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“…Among them, we observed that miR-27a was one of the most dysregulated miRNAs, which has been shown to have a protective effect in many injury models [22][23][24]. Furthermore, miR-27a has been demonstrated to play an important role in regulating inflammatory response [24][25][26]. However, whether miR-27a plays a similar role in ALI remains unknown.…”

Section: Mir-27a Was Downregulated In Lps-induced Acute Lung Injury Imentioning

confidence: 99%

MicroRNA-27a alleviates LPS-induced acute lung injury in mice via inhibiting inﬂammation and apoptosis through modulating TLR4/MyD88/NF-κB pathway

et al. 2018

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Acute lung injury (ALI) is a critical clinical condition with a high mortality rate, characterized with excessive uncontrolled inflammation and apoptosis. Recently, microRNAs (miRNAs) have been found to play crucial roles in the amelioration of various inflammation-induced diseases, including ALI. However, it remains unknown the biological function and regulatory mechanisms of miRNAs in the regulation of inﬂammation and apoptosis in ALI. The aim of this study is to identify and evaluate the potential role of miRNAs in ALI and reveal the underlying molecular mechanisms of their effects. Here, we analyzed microRNA expression profiles in lung tissues from LPS-challenged mice using miRNA microarray. Because microRNA-27a (miR-27a) was one of the miRNAs being most significantly downregulated, which has an important role in regulation of inflammation, we investigated its function. Overexpression of miR-27a by agomir-27a improved lung injury, as evidenced by the reduced histopathological changes, lung wet/dry (W/D) ratio, lung microvascular permeability and apoptosis in the lung tissues, as well as ameliorative survival of ALI mice. This was accompanied by the alleviating of inflammation, such as the reduced total BALF cell and neutrophil counts, decreased levels of tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-6) interleukin-1β (IL-1β) and myeloperoxidase (MPO) activity in BAL fluid. Toll-like receptor 4 (TLR4), an important regulator of the nuclear factor kappa-B (NF-κB) signaling pathway, was identified as a novel target of miR-27a in RAW264.7 cells. Furthermore, our results showed that LPS stimulation increased the expression of MyD88 and NF-κB p65 (p-p65), but inhibited the expression of inhibitor of nuclear factor-κB-α (IκB-α), suggesting the activation of NF-κB signaling pathway. Further investigations revealed that agomir-miR-27a reversed the promoting effect of LPS on NF-κB signaling pathway. The results here suggested that miR-27a alleviates LPS-induced ALI in mice via reducing inﬂammation and apoptosis through blocking TLR4/MyD88/NF-κB activation.

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Mmu-miR-27a-5p-Dependent Upregulation of MCPIP1 Inhibits the Inflammatory Response in LPS-Induced RAW264.7 Macrophage Cells

Cited by 26 publications

References 25 publications

miR-27a protects human mitral valve interstitial cell from TNF-α-induced inflammatory injury via up-regulation of NELL-1

miR-27a protects human mitral valve interstitial cell from TNF-α-induced inflammatory injury via up-regulation of NELL-1

Regnase-1, a rapid response ribonuclease regulating inflammation and stress responses

MicroRNA-27a alleviates LPS-induced acute lung injury in mice via inhibiting inﬂammation and apoptosis through modulating TLR4/MyD88/NF-κB pathway

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