MicroRNA gga-miR-200a-3p modulates immune response via MAPK signaling pathway in chicken afflicted with necrotic enteritis

• Published in: Veterinary research (Paris) Vol. 51; no. 1; p. 8
• Main Authors: Pham, Thu Thao, Ban, Jihye, Hong, Yeojin, Lee, Jiae, Vu, Thi Hao, Truong, Anh Duc, Lillehoj, Hyun S, Hong, Yeong Ho
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.02.2020; BioMed Central; BMC
• Subjects: Agricultural research; Antimicrobial agents; Binding sites; Cloning; Cytomegalovirus; Disease; Disease susceptibility; Diseases; Enteritis; Fluorescence; Genes; Health aspects; Immune response; Infection; Life Sciences; Liver cancer; Luciferase; Macrophages; MicroRNA; MicroRNAs; Mitogens; Plasmids; Poultry; Protein kinases; Proteins; Scientific equipment industry; Transcription (Genetics); Transforming growth factors; United States; United States > US; South Korea
• ISSN: 1297-9716; 0928-4249; 1297-9716
• DOI: 10.1186/s13567-020-0736-x

MicroRNAs (miRNAs) are small non-coding RNAs that contribute to host immune response as post-transcriptional regulation. The current study investigated the biological role of the chicken (Gallus gallus) microRNA-200a-3p (gga-miR-200a-3p), using 2 necrotic enteritis (NE) afflicted genetically disparate chicken lines, 6.3 and 7.2, as well as the mechanisms underlying the fundamental signaling pathways in chicken. The expression of gga-miR-200a-3p in the intestinal mucosal layer of NE-induced chickens, was found to be upregulated during NE infection in the disease-susceptible chicken line 7.2. To validate the target genes, we performed an overexpression analysis of gga-miR-200a-3p using chemically synthesized oligonucleotides identical to gga-miR-200a-3p, reporter gene analysis including luciferase reporter assay, and a dual fluorescence reporter assay in cultured HD11 chicken macrophage cell lines. Gga-miR-200a-3p was observed to be a direct transcriptional repressor of ZAK, MAP2K4, and TGFβ2 that are involved in mitogen-activated protein kinase (MAPK) pathway by targeting the 3'-UTR of their transcripts. Besides, gga-miR-200a-3p may indirectly affect the expression of protein kinases including p38 and ERK1/2 at both transcriptional and translational levels, suggesting that this miRNA may function as an important regulator of the MAPK signaling pathway. Proinflammatory cytokines consisting of IL-1β, IFN-γ, IL-12p40, IL-17A, and LITAF belonging to Th1 and Th17-type cytokines, were upregulated upon gga-miR-200a-3p overexpression. These findings have enhanced our knowledge of the immune function of gga-miR-200a-3p mediating the chicken immune response via regulation of the MAPK signaling pathway and indicate that this miRNA may serve as an important biomarker of diseases in domestic animals.