Poly r(C) binding protein 1‐mediated regulation of microRNA expression underlies post‐sevoflurane amelioration of acute lung injury in rats

Zhao, Xiaohong; Wang, Xiaoxia; Wang, Fei; Gao, Chengjie; Wang, Jian

doi:10.1002/jcp.26053

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…Several studies have reported the role of miRNAs as biomarkers of ALI, and their potential use as therapeutic targets for this condition [38][39][40][41]. Microarray data from various experimental models reveal that ALI induces aberrant expression of miRNAs and the potential targets for these miRNAs that are associated with many pathophysiological processes such as inflammation and apoptosis [42,43]. In the present, by using miRNA microarray analyses, we found a large set of miRNAs were significantly deregulated in injured lung tissues compared with normal group, and the expression of miR-27a was further confirmed by qRT-PCR analysis.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…4a, c ). To determine if PCBP1 associates with the rat Hapln2 pre-mRNA, RIP was performed in the hippocampus of both male and female rats, using a PCBP1 antibody [ 29 , 30 ] followed by qPCR using primers surrounding the cytosine rich PCBP1 motif in Hapln2 (Fig. 4a ).…”

Section: Resultsmentioning

confidence: 99%

“…140 μl of clarified supernatant was incubated overnight at 4 °C with 5 μg of mouse monoclonal anti-PCBP1 antibody (AB_2299322, #sc137249, Santa Cruz Biotechnology), and the remaining 40 μl was used as input. PCBP1 antibody has been validated in rat tissue and used for western blot and immunoprecipitation [ 14 , 29 , 30 ]. Positive and negative controls used anti-Hur and anti-IgG antibodies respectively (#03-102 Millipore Sigma).…”

Section: Methodsmentioning

confidence: 99%

Conserved role for PCBP1 in altered RNA splicing in the hippocampus after chronic alcohol exposure

et al. 2023

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We previously discovered using transcriptomics that rats undergoing withdrawal after chronic ethanol exposure had increased expression of several genes encoding RNA splicing factors in the hippocampus. Here, we examined RNA splicing in the rat hippocampus during withdrawal from chronic ethanol exposure and in postmortem hippocampus of human subjects diagnosed with alcohol use disorder (AUD). We found that expression of the gene encoding the splicing factor, poly r(C) binding protein 1 (PCBP1), was elevated in the hippocampus of rats during withdrawal after chronic ethanol exposure and AUD subjects. We next analyzed the rat RNA-Seq data for differentially expressed (DE) exon junctions. One gene, Hapln2, had increased usage of a novel 3′ splice site in exon 4 during withdrawal. This splice site was conserved in human HAPLN2 and was used more frequently in the hippocampus of AUD compared to control subjects. To establish a functional role for PCBP1 in HAPLN2 splicing, we performed RNA immunoprecipitation (RIP) with a PCBP1 antibody in rat and human hippocampus, which showed enriched PCBP1 association near the HAPLN2 exon 4 3′ splice site in the hippocampus of rats during ethanol withdrawal and AUD subjects. Our results indicate a conserved role for the splicing factor PCBP1 in aberrant splicing of HAPLN2 after chronic ethanol exposure. As the HAPLN2 gene encodes an extracellular matrix protein involved in nerve conduction velocity, use of this alternative splice site is predicted to result in loss of protein function that could negatively impact hippocampal function in AUD.

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“…Fu et al [ 91 ] reported that LPS further enhanced the upregulation of miR-155 in the prostatic tissues of mice with experimental autoimmune prostatitis. In a LPS-induced acute lung injury animal model, miR-155 expression was found to be significantly upregulated in the lungs of mice and rats, and reached a peak at 6 h of LPS stimulation [ 128 , 129 ]. Bala et al [ 130 ] also observed an increase of miR-155 levels in the livers of WT mice following LPS or alcohol treatment, which was significantly eliminated by knockout of TLR4.…”

Section: Inductive Effect Of Tlr4 Activation On Mir-155mentioning

confidence: 99%

TLR4 signaling in the development of colitis-associated cancer and its possible interplay with microRNA-155

2021

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Ulcerative colitis (UC) has closely been associated with an increased risk of colorectal cancer. However, the exact mechanisms underlying colitis-associated cancer (CAC) development remain unclear. As a classic pattern-recognition receptor, Toll like receptor (TLR)4 is a canonical receptor for lipopolysaccharide of Gram-negative bacteria (including two CAC-associated pathogens Fusobacterium nucleatum and Salmonella), and functions as a key bridge molecule linking oncogenic infection to colonic inflammatory and malignant processes. Accumulating studies verified the overexpression of TLR4 in colitis and CAC, and the over-expressed TLR4 might promote colitis-associated tumorigenesis via facilitating cell proliferation, protecting malignant cells against apoptosis, accelerating invasion and metastasis, as well as contributing to the creation of tumor-favouring cellular microenvironment. In recent years, considerable attention has been focused on the regulation of TLR4 signaling in the context of colitis-associated tumorigenesis. MicroRNA (miR)-155 and TLR4 exhibited a similar dynamic expression change during CAC development and shared similar CAC-promoting properties. The available data demonstrated an interplay between TLR4 and miR-155 in the context of different disorders or cell lines. miR-155 could augment TLR4 signaling through targeting negative regulators SOCS1 and SHIP1; and TLR4 activation would induce miR-155 expression via transcriptional and post-transcriptional mechanisms. This possible TLR4-miR-155 positive feedback loop might result in the synergistic accelerating effect of TLR4 and miR-155 on CAC development.

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Poly r(C) binding protein 1‐mediated regulation of microRNA expression underlies post‐sevoflurane amelioration of acute lung injury in rats

Cited by 5 publications

References 24 publications

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

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

Conserved role for PCBP1 in altered RNA splicing in the hippocampus after chronic alcohol exposure

TLR4 signaling in the development of colitis-associated cancer and its possible interplay with microRNA-155

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