miR-146a-5p promotes epithelium regeneration against LPS-induced inflammatory injury via targeting TAB1/TAK1/NF-κB signaling pathway

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.