Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China; Key Laboratory of Animal Nutrition in Jiangxi Province, Jiangxi Agricultural University, Nanchang, China.
Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China.
Int J Biol Macromol. 2022 Nov 30;221:1031-1040. doi: 10.1016/j.ijbiomac.2022.09.056. Epub 2022 Sep 10.
Intestinal inflammation often restricts the health and production of animals. MiR-146a has been proved to be an anti-inflammatory molecule in inflammatory disorders, but its role in the intestinal injury and regeneration remains unclear. The study aimed to explore the inflammatory response of intestinal epithelial cells (IECs) in intestinal tissue-specific miR-146a-5p knockout mouse models. We identified the role of miR-146a-5p in inhibiting inflammatory response and promoting proliferation under lipopolysaccharide (LPS) stimulation in vitro and vivo. LPS stimulation significantly increased the expression of TNF-α, IL6 and inhibited IPEC-J2 cell proliferation. Overexpression of miR-146a-5p can reverse the effect of LPS stimulation, and promote the proliferation of intestinal epithelial cells. In the LPS challenge experiment in intestine-specific miR-146a knock-out mice (CKO) and Floxp mice (CON), CKO mice were more sensitive to LPS stimulation, with more weight loss and more severe intestinal morphological damage than CON mice. Also, miR-146a-5p regulated LPS-induced intestinal injury, inflammation by targeting TAB1. Taken together, miR-146a may function as an anti-inflammatory factor in IECs by targeting TAB1/TAK1-IKK-NF-κB signaling pathway. miR-146a-5p may represent a promising biomarker for inflammatory disorders, and may provide an effective therapeutic method to alleviate weaning stress in piglets and some experimental basis to improve the intestinal health of livestock.
肠道炎症常限制动物的健康和生产。miR-146a 已被证明在炎症性疾病中是一种抗炎分子，但它在肠道损伤和再生中的作用尚不清楚。本研究旨在探讨肠道组织特异性 miR-146a-5p 敲除小鼠模型中肠道上皮细胞（IECs）的炎症反应。我们确定了 miR-146a-5p 在体外和体内抑制脂多糖（LPS）刺激下的炎症反应和促进增殖的作用。LPS 刺激显著增加了 TNF-α、IL6 的表达，并抑制了 IPEC-J2 细胞的增殖。miR-146a-5p 的过表达可以逆转 LPS 刺激的作用，并促进肠上皮细胞的增殖。在肠道特异性 miR-146a 敲除小鼠（CKO）和 Floxp 小鼠（CON）的 LPS 挑战实验中，CKO 小鼠对 LPS 刺激更敏感，体重下降更多，肠道形态损伤比 CON 小鼠更严重。此外，miR-146a-5p 通过靶向 TAB1 调节 LPS 诱导的肠道损伤和炎症。总之，miR-146a 可能通过靶向 TAB1/TAK1-IKK-NF-κB 信号通路在 IECs 中发挥抗炎因子的作用。miR-146a-5p 可能成为炎症性疾病有前途的生物标志物，并可能为减轻仔猪断奶应激提供有效的治疗方法，为改善家畜肠道健康提供一些实验基础。
