MicroRNA gga-miR-10a-mediated transcriptional regulation of the immune genes in necrotic enteritis afflicted chickens

miRNAs are involved in both adaptive and innate immune systems of host animals; and play important roles in many immune-related pathways. The systemic biological roles of gga-miR-10a-5p chicken microRNA on immune response were investigated in two necrotic enteritis (NE) induced chicken lines, Marek&...

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Veröffentlicht in:Developmental and comparative immunology 2020-01, Vol.102, p.103472-103472, Article 103472
Hauptverfasser: Pham, Thu Thao, Ban, Jihye, Lee, Kyungbaek, Hong, Yeojin, Lee, Jiae, Truong, Anh Duc, Lillehoj, Hyun S., Hong, Yeong Ho
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container_title Developmental and comparative immunology
container_volume 102
creator Pham, Thu Thao
Ban, Jihye
Lee, Kyungbaek
Hong, Yeojin
Lee, Jiae
Truong, Anh Duc
Lillehoj, Hyun S.
Hong, Yeong Ho
description miRNAs are involved in both adaptive and innate immune systems of host animals; and play important roles in many immune-related pathways. The systemic biological roles of gga-miR-10a-5p chicken microRNA on immune response were investigated in two necrotic enteritis (NE) induced chicken lines, Marek's disease (MD) resistant (line 6.3) and susceptible (line 7.2). We determined the expression patterns of gga-miR-10a in the intestinal mucosal layer of chickens upon NE induction, and identified the target genes (MyD88, and SKP1) related to the host immune response to pathogens. We found that gga-miR-10a expression in the intestinal mucosal layer of MD-resistant chicken line 6.3 gga-miR-10a was significantly down-regulated (p 
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The systemic biological roles of gga-miR-10a-5p chicken microRNA on immune response were investigated in two necrotic enteritis (NE) induced chicken lines, Marek's disease (MD) resistant (line 6.3) and susceptible (line 7.2). We determined the expression patterns of gga-miR-10a in the intestinal mucosal layer of chickens upon NE induction, and identified the target genes (MyD88, and SKP1) related to the host immune response to pathogens. We found that gga-miR-10a expression in the intestinal mucosal layer of MD-resistant chicken line 6.3 gga-miR-10a was significantly down-regulated (p &lt; 0.01) during NE. Overexpression analysis of gga-miR-10a and reporter gene analysis using a wild- or mutant-type MyD88 3′ untranslated region (3′ UTR)-luciferase construct in chicken macrophage cell line HD11 and chicken fibroblast cell line OU2 showed that gga-miR-10a acted as a direct translational repressor of MyD88 by targeting the 3′ UTR of this gene. Furthermore, miR-10a indirectly negatively influenced the expression of signaling molecules related to the MyD88-dependent pathway, including TRAF6, TAK1, and NF-κB1 at both transcriptional and translational levels. Downstream of the MyD88-dependent pathway, several proinflammatory cytokines such as IL-1β, IFN-γ, IL-12p40, TNFSF15, and LITAF were down-regulated by overexpression of gga-miR-10a. These results suggest that gga-miR-10a is an important regulator of the Toll-like receptor signaling pathway. The findings of this study improve our understanding of the biological functions of miR-10a and the mechanisms underlying the TLR signaling pathway upon NE afflicted chickens, as well improving the overall understanding of the immune system function in domestic animals. •Gga-miR-10a significantly down-regulated in the resistant line 6.3 compared to the susceptible line 7.2 induced by NE.•Gga-miR-10a directly suppressed the expression level of its target gene MyD88.•Gga-miR-10a inhibited the expression of the signaling molecules as the downstream of MyD88-dependent pathway.•Gga-miR-10a indirectly repressed Th1, and pro-inflammatory cytokine production.</description><identifier>ISSN: 0145-305X</identifier><identifier>EISSN: 1879-0089</identifier><identifier>DOI: 10.1016/j.dci.2019.103472</identifier><identifier>PMID: 31437523</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>3' Untranslated regions ; Adaptive systems ; Animals ; Biotechnology ; Chicken ; Chickens ; Cytokines ; Domestic animals ; Enteritis ; Gene expression ; Gene regulation ; Genes ; IL-1β ; Immune response ; Immune system ; Inflammation ; Innate immunity ; Interleukin 12 ; Intestine ; Macrophages ; Marek's disease ; MicroRNAs ; miR-10a ; miRNA ; Mucosa ; MyD88 ; MyD88 protein ; Necrotic enteritis ; Poultry ; Reporter gene ; Ribonucleic acid ; RNA ; Signal transduction ; Signaling ; TAK1 protein ; Target recognition ; Toll-like receptor signaling pathway ; Toll-like receptors ; TRAF6 protein ; Transcription ; Translation ; γ-Interferon</subject><ispartof>Developmental and comparative immunology, 2020-01, Vol.102, p.103472-103472, Article 103472</ispartof><rights>2019 Elsevier Ltd</rights><rights>Copyright © 2019 Elsevier Ltd. 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The systemic biological roles of gga-miR-10a-5p chicken microRNA on immune response were investigated in two necrotic enteritis (NE) induced chicken lines, Marek's disease (MD) resistant (line 6.3) and susceptible (line 7.2). We determined the expression patterns of gga-miR-10a in the intestinal mucosal layer of chickens upon NE induction, and identified the target genes (MyD88, and SKP1) related to the host immune response to pathogens. We found that gga-miR-10a expression in the intestinal mucosal layer of MD-resistant chicken line 6.3 gga-miR-10a was significantly down-regulated (p &lt; 0.01) during NE. Overexpression analysis of gga-miR-10a and reporter gene analysis using a wild- or mutant-type MyD88 3′ untranslated region (3′ UTR)-luciferase construct in chicken macrophage cell line HD11 and chicken fibroblast cell line OU2 showed that gga-miR-10a acted as a direct translational repressor of MyD88 by targeting the 3′ UTR of this gene. 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The findings of this study improve our understanding of the biological functions of miR-10a and the mechanisms underlying the TLR signaling pathway upon NE afflicted chickens, as well improving the overall understanding of the immune system function in domestic animals. •Gga-miR-10a significantly down-regulated in the resistant line 6.3 compared to the susceptible line 7.2 induced by NE.•Gga-miR-10a directly suppressed the expression level of its target gene MyD88.•Gga-miR-10a inhibited the expression of the signaling molecules as the downstream of MyD88-dependent pathway.•Gga-miR-10a indirectly repressed Th1, and pro-inflammatory cytokine production.</description><subject>3' Untranslated regions</subject><subject>Adaptive systems</subject><subject>Animals</subject><subject>Biotechnology</subject><subject>Chicken</subject><subject>Chickens</subject><subject>Cytokines</subject><subject>Domestic animals</subject><subject>Enteritis</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>IL-1β</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Inflammation</subject><subject>Innate immunity</subject><subject>Interleukin 12</subject><subject>Intestine</subject><subject>Macrophages</subject><subject>Marek's disease</subject><subject>MicroRNAs</subject><subject>miR-10a</subject><subject>miRNA</subject><subject>Mucosa</subject><subject>MyD88</subject><subject>MyD88 protein</subject><subject>Necrotic enteritis</subject><subject>Poultry</subject><subject>Reporter gene</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>TAK1 protein</subject><subject>Target recognition</subject><subject>Toll-like receptor signaling pathway</subject><subject>Toll-like receptors</subject><subject>TRAF6 protein</subject><subject>Transcription</subject><subject>Translation</subject><subject>γ-Interferon</subject><issn>0145-305X</issn><issn>1879-0089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kU9rFEEQxRsxmE30A3iRBi9eZu2_O914CiEaISYQInhrenpqNr3O9KzdPYLf3lo2evBgXYqCX73i1SPkNWdrzvjm_W7dh7gWjFucpWrFM7LiprUNY8Y-JyvGlW4k099OyVkpO4ZlOHtBTiVXstVCrsjyJYY8399e0O3WN1O8bzjDDn30FXpas08l5LivcU5-pBm2y-gPA50HWh-BxmlaEtAtJCg0JpoA9WoMFFKFHGss1A_DGMNBLjzG8B1SeUlOBj8WePXUz8nXj1cPl9fNzd2nz5cXN01QQtWm66xgrdIGvSnZt3YYpNDcmM53aFNYZXvjlbK211aJAQYN3gZmDDfeWinPybuj7j7PPxYo1U2xBBhHn2BeihPCML3RylhE3_6D7uYlo2ekJMermm0MUvxIoclSMgxun-Pk8y_HmTtk4nYOM3GHTNwxE9x586S8dPjYvxt_QkDgwxEAfMXPCNmVECEFDCFDqK6f43_kfwP1zJty</recordid><startdate>202001</startdate><enddate>202001</enddate><creator>Pham, Thu Thao</creator><creator>Ban, Jihye</creator><creator>Lee, Kyungbaek</creator><creator>Hong, Yeojin</creator><creator>Lee, Jiae</creator><creator>Truong, Anh Duc</creator><creator>Lillehoj, Hyun S.</creator><creator>Hong, Yeong Ho</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T5</scope><scope>C1K</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>202001</creationdate><title>MicroRNA gga-miR-10a-mediated transcriptional regulation of the immune genes in necrotic enteritis afflicted chickens</title><author>Pham, Thu Thao ; 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and play important roles in many immune-related pathways. The systemic biological roles of gga-miR-10a-5p chicken microRNA on immune response were investigated in two necrotic enteritis (NE) induced chicken lines, Marek's disease (MD) resistant (line 6.3) and susceptible (line 7.2). We determined the expression patterns of gga-miR-10a in the intestinal mucosal layer of chickens upon NE induction, and identified the target genes (MyD88, and SKP1) related to the host immune response to pathogens. We found that gga-miR-10a expression in the intestinal mucosal layer of MD-resistant chicken line 6.3 gga-miR-10a was significantly down-regulated (p &lt; 0.01) during NE. Overexpression analysis of gga-miR-10a and reporter gene analysis using a wild- or mutant-type MyD88 3′ untranslated region (3′ UTR)-luciferase construct in chicken macrophage cell line HD11 and chicken fibroblast cell line OU2 showed that gga-miR-10a acted as a direct translational repressor of MyD88 by targeting the 3′ UTR of this gene. Furthermore, miR-10a indirectly negatively influenced the expression of signaling molecules related to the MyD88-dependent pathway, including TRAF6, TAK1, and NF-κB1 at both transcriptional and translational levels. Downstream of the MyD88-dependent pathway, several proinflammatory cytokines such as IL-1β, IFN-γ, IL-12p40, TNFSF15, and LITAF were down-regulated by overexpression of gga-miR-10a. These results suggest that gga-miR-10a is an important regulator of the Toll-like receptor signaling pathway. The findings of this study improve our understanding of the biological functions of miR-10a and the mechanisms underlying the TLR signaling pathway upon NE afflicted chickens, as well improving the overall understanding of the immune system function in domestic animals. •Gga-miR-10a significantly down-regulated in the resistant line 6.3 compared to the susceptible line 7.2 induced by NE.•Gga-miR-10a directly suppressed the expression level of its target gene MyD88.•Gga-miR-10a inhibited the expression of the signaling molecules as the downstream of MyD88-dependent pathway.•Gga-miR-10a indirectly repressed Th1, and pro-inflammatory cytokine production.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>31437523</pmid><doi>10.1016/j.dci.2019.103472</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects 3' Untranslated regions
Adaptive systems
Animals
Biotechnology
Chicken
Chickens
Cytokines
Domestic animals
Enteritis
Gene expression
Gene regulation
Genes
IL-1β
Immune response
Immune system
Inflammation
Innate immunity
Interleukin 12
Intestine
Macrophages
Marek's disease
MicroRNAs
miR-10a
miRNA
Mucosa
MyD88
MyD88 protein
Necrotic enteritis
Poultry
Reporter gene
Ribonucleic acid
RNA
Signal transduction
Signaling
TAK1 protein
Target recognition
Toll-like receptor signaling pathway
Toll-like receptors
TRAF6 protein
Transcription
Translation
γ-Interferon
title MicroRNA gga-miR-10a-mediated transcriptional regulation of the immune genes in necrotic enteritis afflicted chickens
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