Nannan Yin1, Yaping Yang1, Xiaoyan Wang1, Chao Yang1, Xiaofei Ma1, Aftab Shaukat1, Gan Zhao1, Ganzhen Deng2. 1. Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. 2. Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. ganzhendeng@sohu.com.
Abstract
OBJECTIVE: In both humans and animals, endometritis is severe inflammation of the uterus, and it causes great economic losses in dairy cow production. MicroRNAs have been reported to play an important role in various inflammatory diseases. However, the regulatory mechanisms of miR-19a in endometritis remain unclear. Thus, the aims of this study are to investigate the role of miR-19a in a mouse model of lipopolysaccharide (LPS)-induced endometritis and elucidate the possible mechanisms in bovine endometrial epithelial cells (bEECs). METHODS AND RESULTS: Histological analysis showed that LPS induced severe pathological changes, suggesting that the endometritis mouse model was well established. The qPCR assay indicated that miR-19a expression in the uterine tissues of mice with endometritis and in bEECs with LPS stimulation was significantly reduced. The overexpression of miR-19a significantly decreased the expression of inflammatory cytokines (TNF-α, IL-6 and IL-1β) and the phosphorylation of NF-κB p65 and IκBα. Similar results were also obtained following the knockdown of TBK1. Furthermore, a dual luciferase reporter assay further validated that miR-19a inhibited TBK1 expression by binding directly to the 3'-UTR of TBK1. CONCLUSION: We demonstrated that miR-19a has anti-inflammatory effects and mediates the negative regulation of the NF-κB Pathway in LPS-induced endometritis by targeting TBK1.
OBJECTIVE: In both humans and animals, endometritis is severe inflammation of the uterus, and it causes great economic losses in dairy cow production. MicroRNAs have been reported to play an important role in various inflammatory diseases. However, the regulatory mechanisms of miR-19a in endometritis remain unclear. Thus, the aims of this study are to investigate the role of miR-19a in a mouse model of lipopolysaccharide (LPS)-induced endometritis and elucidate the possible mechanisms in bovine endometrial epithelial cells (bEECs). METHODS AND RESULTS: Histological analysis showed that LPS induced severe pathological changes, suggesting that the endometritismouse model was well established. The qPCR assay indicated that miR-19a expression in the uterine tissues of mice with endometritis and in bEECs with LPS stimulation was significantly reduced. The overexpression of miR-19a significantly decreased the expression of inflammatory cytokines (TNF-α, IL-6 and IL-1β) and the phosphorylation of NF-κB p65 and IκBα. Similar results were also obtained following the knockdown of TBK1. Furthermore, a dual luciferase reporter assay further validated that miR-19a inhibited TBK1 expression by binding directly to the 3'-UTR of TBK1. CONCLUSION: We demonstrated that miR-19a has anti-inflammatory effects and mediates the negative regulation of the NF-κB Pathway in LPS-induced endometritis by targeting TBK1.
Authors: S J LeBlanc; T F Duffield; K E Leslie; K G Bateman; G P Keefe; J S Walton; W H Johnson Journal: J Dairy Sci Date: 2002-09 Impact factor: 4.034
Authors: Brent C Credille; Amelia R Woolums; Michael W Overton; David J Hurley; Steeve Giguère Journal: Res Vet Sci Date: 2015-05-27 Impact factor: 2.534
Authors: Erica Marchlik; Paresh Thakker; Thaddeus Carlson; Zhaozhao Jiang; Mark Ryan; Suzana Marusic; Nadege Goutagny; Wen Kuang; G Roger Askew; Victoria Roberts; Stephen Benoit; Tianhui Zhou; Vincent Ling; Richard Pfeifer; Nancy Stedman; Katherine A Fitzgerald; Lih-Ling Lin; J Perry Hall Journal: J Leukoc Biol Date: 2010-07-22 Impact factor: 4.962
Authors: I Haj-Salem; R Fakhfakh; J-C Bérubé; E Jacques; S Plante; M J Simard; Y Bossé; J Chakir Journal: Allergy Date: 2014-12-19 Impact factor: 13.146