Transcriptomic analysis identifies Toll‐like and Nod‐like pathways and necroptosis in pulmonary arterial hypertension

Xiao, Genfa; Zhuang, Wenxin; Wang, Tingjun; Lian, Guili; Lu, Luo; Ye, Chaoyi; Wang, Huajun; Xie, Liangdi

doi:10.1111/jcmm.15745

Cited by 37 publications

(37 citation statements)

References 62 publications

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“…Evidence from many clinical and basic studies suggests that inflammatory injury plays a causal role in the pathogenesis of pulmonary vascular remodeling and PAH ( 2 , 5 ). The infiltration of inflammatory and immune cells, such as macrophages, lymphocytes, dendritic cells, and mast cells, has been identified in the pulmonary tissue of patients with PAH ( 6 ). In particular, macrophages and macrophage-derived inflammatory mediators are essential for PAH progression ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Donepezil Ameliorates Pulmonary Arterial Hypertension by Inhibiting M2-Macrophage Activation

Qiu

Zhang

et al. 2021

Front. Cardiovasc. Med.

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Background: The beneficial effects of parasympathetic stimulation in pulmonary arterial hypertension (PAH) have been reported. However, the specific mechanism has not been completely clarified. Donepezil, an oral cholinesterase inhibitor, enhances parasympathetic activity by inhibiting acetylcholinesterase, whose therapeutic effects in PAH and its mechanism deserve to be investigated.Methods: The PAH model was established by a single intraperitoneal injection of monocrotaline (MCT, 50 mg/kg) in adult male Sprague-Dawley rats. Donepezil was administered via intraperitoneal injection daily after 1 week of MCT administration. At the end of the study, PAH status was confirmed by echocardiography and hemodynamic measurement. Testing for acetylcholinesterase activity and cholinergic receptor expression was used to evaluate parasympathetic activity. Indicators of pulmonary arterial remodeling and right ventricular (RV) dysfunction were assayed. The proliferative and apoptotic ability of pulmonary arterial smooth muscle cells (PASMCs), inflammatory reaction, macrophage infiltration in the lung, and activation of bone marrow-derived macrophages (BMDMs) were also tested. PASMCs from the MCT-treated rats were co-cultured with the supernatant of BMDMs treated with donepezil, and then, the proliferation and apoptosis of PASMCs were evaluated.Results: Donepezil treatment effectively enhanced parasympathetic activity. Furthermore, it markedly reduced mean pulmonary arterial pressure and RV systolic pressure in the MCT-treated rats, as well as reversed pulmonary arterial remodeling and RV dysfunction. Donepezil also reduced the proliferation and promoted the apoptosis of PASMCs in the MCT-treated rats. In addition, it suppressed the inflammatory response and macrophage activation in both lung tissue and BMDMs in the model rats. More importantly, donepezil reduced the proliferation and promoted the apoptosis of PASMCs by suppressing M2-macrophage activation.Conclusion: Donepezil could prevent pulmonary vascular and RV remodeling, thereby reversing PAH progression. Moreover, enhancement of the parasympathetic activity could reduce the proliferation and promote the apoptosis of PASMCs in PAH by suppressing M2-macrophage activation.

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Section: Introductionmentioning

confidence: 99%

Donepezil Ameliorates Pulmonary Arterial Hypertension by Inhibiting M2-Macrophage Activation

Qiu

Zhang

et al. 2021

Front. Cardiovasc. Med.

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“…Each was then subsetted to 100,000 reads. Human: Single-end, reverse: SRS7176970 and SRS7176971 [ 65 ] Single-end, forward: ERS2758385 and ERS2758384 Paired-end reverse: SRS5027402 and SRS5027403 [ 66 ] Paired-end forward: samples dm3_file1 and dm3_file2 from Rail-RNA [ 67 ]; samples sample_01 and sample_02 generated with polyester [ 64 ] Mouse Single-end, reverse: SRS7205735 and ERS3517668 Single-end, forward: all files generated with polyester [ 64 ] Paired-end, reverse: SRS7160912 and SRS7160911 Paired-end, forward: all files generated with polyester [ 64 ] Rat Single-end, reverse: SRS6431375 Single-end, forward: all files generated with polyester [ 64 ] Paired-end, reverse: SRS6590988 and SRS6590989 [ 68 ] Paired-end, forward: all files generated with polyester [ 64 ] …”

Section: Methodsmentioning

confidence: 99%

“…Rat Single-end, reverse: SRS6431375 Single-end, forward: all files generated with polyester [ 64 ] Paired-end, reverse: SRS6590988 and SRS6590989 [ 68 ] Paired-end, forward: all files generated with polyester [ 64 ] …”

Section: Methodsmentioning

confidence: 99%

SPEAQeasy: a scalable pipeline for expression analysis and quantification for R/bioconductor-powered RNA-seq analyses

Eagles

Burke

Leonard³

et al. 2021

BMC Bioinformatics

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Background RNA sequencing (RNA-seq) is a common and widespread biological assay, and an increasing amount of data is generated with it. In practice, there are a large number of individual steps a researcher must perform before raw RNA-seq reads yield directly valuable information, such as differential gene expression data. Existing software tools are typically specialized, only performing one step–such as alignment of reads to a reference genome–of a larger workflow. The demand for a more comprehensive and reproducible workflow has led to the production of a number of publicly available RNA-seq pipelines. However, we have found that most require computational expertise to set up or share among several users, are not actively maintained, or lack features we have found to be important in our own analyses. Results In response to these concerns, we have developed a Scalable Pipeline for Expression Analysis and Quantification (SPEAQeasy), which is easy to install and share, and provides a bridge towards R/Bioconductor downstream analysis solutions. SPEAQeasy is portable across computational frameworks (SGE, SLURM, local, docker integration) and different configuration files are provided (http://research.libd.org/SPEAQeasy/). Conclusions SPEAQeasy is user-friendly and lowers the computational-domain entry barrier for biologists and clinicians to RNA-seq data processing as the main input file is a table with sample names and their corresponding FASTQ files. The goal is to provide a flexible pipeline that is immediately usable by researchers, regardless of their technical background or computing environment.

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“…In this study, based on the gene annotation and the metabolic pathway analysis of the skin transcriptome, the coding genes annotated the NLR-signaling pathway were blasted on NCBI, the transcripts were found to have very high consistency with sequence from the sperm whale RefSeq genome. Meanwhile, the NLR-signaling pathway was studied in the other species (human, mice, and fish) [ 53 , 60 , 61 ], it was speculated that the NLR-signaling pathway was extremely likely to be annotated in the sperm whale. The NOD1/NOD2 recognized the bacterial PGN and then transmitted and stimulated immune signals, which generated several central immune factors, immune substances, and antimicrobial peptides that played significant roles in the body’s immune responses ( Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated Full-Length Transcriptome and RNA-Seq to Identify Immune System Genes from the Skin of Sperm Whale (Physeter macrocephalus)

Wang

Aierken

et al. 2021

Genes

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Cetaceans are a group of secondary aquatic mammals whose ancestors returned to the ocean from land, and during evolution, their immune systems adapted to the aquatic environment. Their skin, as the primary barrier to environmental pathogens, supposedly evolved to adapt to a new living environment. However, the immune system in the skin of cetaceans and the associated molecular mechanisms are still largely unknown. To better understand the immune system, we extracted RNA from the sperm whale’s (Physeter macrocephalus) skin and performed PacBio full-length sequencing and RNA-seq sequencing. We obtained a total of 96,350 full-length transcripts with an average length of 1705 bp and detected 5150 genes that were associated with 21 immune-related pathways by gene annotation enrichment analysis. Moreover, we found 89 encoding genes corresponding to 33 proteins were annotated in the NOD-like receptor (NLR)-signaling pathway, including NOD1, NOD2, RIP2, and NF-kB genes, which were discussed in detail and predicted to play essential roles in the immune system of the sperm whale. Furthermore, NOD1 was highly conservative during evolution by the sequence comparison and phylogenetic tree. These results provide new information about the immune system in the skin of cetaceans, as well as the evolution of immune-related genes.

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Transcriptomic analysis identifies Toll‐like and Nod‐like pathways and necroptosis in pulmonary arterial hypertension

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 37 publications

References 62 publications

Donepezil Ameliorates Pulmonary Arterial Hypertension by Inhibiting M2-Macrophage Activation

Donepezil Ameliorates Pulmonary Arterial Hypertension by Inhibiting M2-Macrophage Activation

SPEAQeasy: a scalable pipeline for expression analysis and quantification for R/bioconductor-powered RNA-seq analyses

Integrated Full-Length Transcriptome and RNA-Seq to Identify Immune System Genes from the Skin of Sperm Whale (Physeter macrocephalus)

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