scholarly journals Histone Acetyltransferase Mof Affects the Progression of DSS-Induced Colitis

2018 ◽  
Vol 47 (5) ◽  
pp. 2159-2169 ◽  
Author(s):  
Yang Yang ◽  
Jingyun Guan ◽  
Abdul Sami Shaikh ◽  
Yiran Liang ◽  
Lichao Sun ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Histone Acetyltransferase ◽  
Experimental Colitis ◽  
Conditional Knockout ◽  
Rna Seq ◽  
Histone H4 ◽  
Expression Of Genes ◽  
Differential Expression Of Genes

Background/Aims: Histone acetylation has been demonstrated to be associated with inflammation response. Histone acetyltransferase (HAT) Mof, specifically acetylating lysine 16 of histone H4 (H4K16), has been reported to regulate T cell differentiation. In addition, it has been suggested that acetylation of H4K16 is associated with the inflammatory response. We evaluated the role and potential mechanism of Mof in the development of experimental colitis. Methods: We used Mof conditional knockout mice to study the role of Mof in dextran sulfate sodium (DSS)-induced colitis and detected the differential expression of genes due to Mof deficiency involved in the inflammatory response, particularly the Th17 signaling pathway, by western blotting, quantitative PCR and RNA sequencing (RNA-seq). Results: A significant elevation of Mof was observed in colonic tissues of mice with DSS-induced colitis. Mof deficiency alleviated the severity of DSS- induced colitis in mice. We found that Th17 signaling pathway associated genes, including Il17a, Il22, RORγt, RORα, Stat3, TGF-β 1, and Il6, were downregulated in colon tissues with Mof deficiency. RNA-seq data analysis suggested that 68 genes were related to inflammatory response processing and 47 genes were downregulated in Mof defective colon tissues. Conclusion: Our study demonstrated that HAT Mof is involved in the development of colitis, and the lack of Mof ameliorates DSS-induced colitis in mice.

scholarly journals Role of insulin/insulin-like growth factor-1 signaling pathway genes on the lifespan of Caenorhabditis elegans

2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Siti Bazilah Zulkefli ◽  
Ahmad Nazrun Shuid ◽  
Goon Jo Aan
Keyword(s):  
Caenorhabditis Elegans ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Model Organism ◽  
Insulin Like Growth Factor ◽  
C Elegans ◽  
Expression Of Genes ◽  
Differential Expression Of Genes

Aging process is influenced by the insulin/insulin-like growth factor-1 signaling (IIS) pathway or IGF-1 signaling pathway. Studies done on the genes of this pathway were found to affect longevity. However, no conclusive results have been drawn.The purpose of this systematic review is to summarize the function of genes involved in the IIS pathway of Caenorhabditis Elegans (C. elegans), a nematode commonly used as a model organism in molecular genetics and developmental biology. A literature search for relevant studies was done through PubMed and Scopus databases using MeSH keywords Caenorhabditis elegans, C. elegans, nematode, genes, RNA, DNA, IIS pathway, IGF pathway, lifespan, and longevity. The search was limited to studies that were published in the last ten years (2008-May 2018). After exclusion of duplicates, review papers, human, in vitro, and other organismal studies, a total of 76 research articles were selected for further assessments. Data relevant to the effects of IIS genes on the lifespan ofC. eleganswas independently extracted. Reduction of daf-2 and age-1 and overexpression of sir-2.1 were reported to promote increment of the lifespan of C. elegans.  Furthermore, differentially expressed genes that were involved in the protection against oxidative stress, pathogen attack, and toxicity includeins-18, numr-1/-2, sgk-1, and rgs-1. The knockdown of daf-2, age-1, and overexpression of sir-2.1 genes prolonged the lifespan of C. elegans while knockdown of daf-16, hsf-1, sir-2.1 as well as skn-1 shorten the lifespan of C. elegans.In conclusion, the differential expression of genes in the IIS pathway prolongs the lifespan of C. elegans.

Abstract MP259: The Role Of Sertad4 In Pathological Cardiac Remodeling

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Matthew Stratton ◽  
Ashley Francois ◽  
Oscar Bermeo-Blanco ◽  
Alessandro Canella ◽  
Lynn Marcho ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Systolic Function ◽  
Myocardial Infarct ◽  
Proteasome Inhibition ◽  
Rna Seq ◽  
Expression Of Genes ◽  
M Phase ◽  
Tgf Β1

Over 6 million Americans suffer from heart failure (HF) while the 5-year mortality rate following first admission for HF is over 40%. Cardiac fibrosis is a clinical hallmark of HF, regardless of the initiating pathology and is thought to contribute to disease progression. Using an epigenomics discovery approach, we uncovered a nuclear protein, Sertad4, as a potential anti-fibrotic target. Our data indicate that Sertad4 is a positive regulator of fibroblast activation. Specifically, cultured cardiac fibroblast experiments demonstrate that Sertad4 targeting with shRNAs blocks fibroblast proliferation and causes cells to arrest in the G2/M phase of the cell cycle. Also, shRNA targeting of Sertad4 dramatically blocked activation of myofibroblast differentiation genes (αSMA/POSTN/COL1A1). Mechanistically, these effects appear to be mediated by Sertad4 regulation of SMAD2 protein stability in the presence of TGF-β1 stimulation as demonstrated by proteasome inhibition experiments. RNA-seq analysis indicate that Sertad4 also regulates the expression of genes involved in ubiquitination and proteasome degradation. Next, we sought to determine the effect of global Sertad4 knockout on post-myocardial infarct (MI) remodeling and cardiac function in mice. After 4 weeks of permanent LAD ligation, echocardiography was performed to measure systolic function. Relative to wild-type (WT) controls, the Sertad4 KO mice showed preserved systolic function as evident by improved ejection fraction (WT 14.4 +/- 3.6 vs. KO 33.9+/-5.9, p=0.035) and fractional shortening (WT 6.5 +/- 1.7 vs. KO 16.4 +/- 3.4, p=0.046). β-gal staining in the Sertad4/LacZ reporter mouse subjected to MI showed robust Sertad4/LacZ expression in the ischemic scar and boarder-zone with almost no expression in control hearts. This data supports the notion that Sertad4 has a key role in cardiac remodeling in response to ischemic injury.

scholarly journals Il6/Sil6R Regulates Tnfα-Inflammatory Response In Synovial Fibroblasts Through Modulation of Transcriptional and Post-Transcriptional Mechanisms

2020 ◽  
Author(s):  
Alvaro Valin ◽  
Manuel J. Del Rey ◽  
Cristina Municio ◽  
Alicia Usategui ◽  
Marina Romero ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mononuclear Cells ◽  
De Novo ◽  
Inflammatory Cells ◽  
Synovial Fibroblasts ◽  
Matrix Metalloproteases ◽  
P Value ◽  
Polymorphonuclear Cells ◽  
Expression Of Genes

Abstract Introduction: The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF. Methods SF lines were stimulated with either TNFα or IL6 and sIL6R for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cicloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assesed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value < 0.05 was considered statistically significant. Results IL6/sIL6R stimulation of TNFα treated SF cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.

scholarly journals Study on the role of JAK/STAT signaling pathway during chicken spermatogonial stem cells generation based on RNA-Seq

2015 ◽  
Vol 14 (5) ◽  
pp. 939-948 ◽  
Author(s):  
Lei ZHANG ◽  
Qi-sheng ZUO ◽  
Dong LI ◽  
Chao LIAN ◽  
Kamel E Ahmed ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Spermatogonial Stem Cells ◽  
Rna Seq ◽  
Stat Signaling

CD209 (DC-SIGN) – role in the work of the innate immunity and pathogen penetration

2020 ◽  
Vol 1 (9) ◽  
pp. 64-71
Author(s):  
E. A. Klimov ◽  
◽  
E. K. Novitskaya ◽  
S. N. Koval’chuk ◽  
◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Dendritic Cells ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Adhesion Molecule ◽  
Immune Evasion ◽  
Intercellular Adhesion Molecule ◽  
Lectin Receptor

Intercellular adhesion molecule CD209 (DC-SIGN) is a membrane C-type lectin receptor expressed on the surface of dendritic cells and macrophages. CD209 plays an important role in innate immunity. Many studies have shown the possibility of interaction of the CD209 molecule with a number of dangerous pathogens of humans and animals. This review summarizes information on the structure of the CD209 gene and its product, describes the role of the CD209 protein in the immune response, in the migration of dendritic cells from the blood to the tissue, and their interaction with neutrophils. The currently known signaling pathway of activation through the CD209 inflammatory response is presented. The role of CD209 as an endocytic antigen receptor and the participation of the protein in immune evasion of pathogens are discussed. The mechanisms known to date for the development of infections caused by pathogens of various nature in animals are described.

scholarly journals Differential Expression of Genes Related to the Formation of Giant Leaves in Triploid Poplar

Forests ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 920 ◽  
Author(s):  
Kang Du ◽  
Qiang Han ◽  
Ying Zhang ◽  
Xiangyang Kang
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Leaf Growth ◽  
Growth Hormones ◽  
Endogenous Hormones ◽  
Rna Seq ◽  
Hormone Metabolism ◽  
Expression Of Genes ◽  
Genes Expression ◽  
Differential Expression Of Genes

Plant polyploids tend to have large leaves, but their formation mechanism has not yet been well explained. Therefore, daily transcriptomic differences between triploids and diploids from a synthetic Populus sect. Tacamahaca three times a day (i.e., 04:00, 09:00, and 21:00) were investigated using high-throughput RNA-seq analysis. In this study, we identified several transcription factors associated with giant leaves. The combined effects included the high expression of several transcription factors (WRKY, MYB, etc.) and hormone-related genes (e.g., activates auxin, cytokine, and brassinosteroid synthesis-related genes) that accelerate the synthesis and accumulation of endogenous hormones. High levels of growth hormones were maintained by reducing the genes’ expression of hormone metabolism and degradation. The coordination of hormones accumulated sufficient materials and energy for leaf growth and development. Thereby, cell division and growth were accelerated which enhanced the photosynthesis of leaves, and the increased accumulation of photosynthetic products led to giant triploid leaves. This study lays the foundation for revealing the molecular mechanisms in the formation of giant leaves in polyploids.

scholarly journals BcSas2-Mediated Histone H4K16 Acetylation Is Critical for Virulence and Oxidative Stress Response of Botrytis cinerea

2020 ◽  
Vol 33 (10) ◽  
pp. 1242-1251
Author(s):  
Guangyuan Wang ◽  
Limin Song ◽  
Tingting Bai ◽  
Wenxing Liang
Keyword(s):  
Oxidative Stress ◽  
Botrytis Cinerea ◽  
Target Genes ◽  
Histone Acetyltransferase ◽  
Critical Role ◽  
Rna Seq ◽  
Histone H4 ◽  
Promoter Regions ◽  
Worldwide Distribution ◽  
H4k16 Acetylation

Histone acetyltransferase plays a critical role in transcriptional regulation by increasing accessibility of target genes to transcriptional activators. Botrytis cinerea is an important necrotrophic fungal pathogen with worldwide distribution and a very wide host range, but little is known of how the fungus regulates the transition from saprophytic growth to infectious growth. Here, the function of BcSas2, a histone acetyltransferase of B. cinerea, was investigated. Deletion of the BcSAS2 gene resulted in significantly reduced acetylation levels of histone H4, particularly of H4K16ac. The deletion mutant ΔBcSas2.1 was not only less pathogenic but also more sensitive to oxidative stress than the wild-type strain. RNA-Seq analysis revealed that a total of 13 B. cinerea genes associated with pathogenicity were down-regulated in the ΔBcSas2.1 mutant. Independent knockouts of two of these genes, BcXYGA (xyloglucanase) and BcCAT (catalase), led to dramatically decreased virulence and hypersensitivity to oxidative stress, respectively. Chromatin immunoprecipitation followed by quantitative PCR confirmed that BcSas2 bound directly to the promoter regions of both these pathogenicity-related genes. These observations indicated that BcSas2 regulated the transcription of pathogenicity-related genes by controlling the acetylation level of H4K16, thereby affecting the virulence and oxidative sensitivity of B. cinerea.

scholarly journals Knockout of the OsNAC006 Transcription Factor Causes Drought and Heat Sensitivity in Rice

2020 ◽  
Vol 21 (7) ◽  
pp. 2288 ◽  
Author(s):  
Bo Wang ◽  
Zhaohui Zhong ◽  
Xia Wang ◽  
Xiangyan Han ◽  
Deshui Yu ◽  
...  
Keyword(s):  
Genetic Manipulation ◽  
Heat Sensitivity ◽  
Rna Seq ◽  
Oxidoreductase Activity ◽  
Breeding Programs ◽  
Nac Transcription Factors ◽  
Cofactor Binding ◽  
Expression Of Genes ◽  
Indole 3 Acetic Acid

Rice (Oryza sativa) responds to various abiotic stresses during growth. Plant-specific NAM, ATAF1/2, and CUC2 (NAC) transcription factors (TFs) play an important role in controlling numerous vital growth and developmental processes. To date, 170 NAC TFs have been reported in rice, but their roles remain largely unknown. Herein, we discovered that the TF OsNAC006 is constitutively expressed in rice, and regulated by H2O2, cold, heat, abscisic acid (ABA), indole-3-acetic acid (IAA), gibberellin (GA), NaCl, and polyethylene glycol (PEG) 6000 treatments. Furthermore, knockout of OsNAC006 using the CRISPR-Cas9 system resulted in drought and heat sensitivity. RNA sequencing (RNA-seq) transcriptome analysis revealed that OsNAC006 regulates the expression of genes mainly involved in response to stimuli, oxidoreductase activity, cofactor binding, and membrane-related pathways. Our findings elucidate the important role of OsNAC006 in drought responses, and provide valuable information for genetic manipulation to enhance stress tolerance in future plant breeding programs.

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