Liu Haokun, Zhao Ying, Wu Yanfang, Yan Yutong, Zhao Xiaoe, Wei Qiang, Ma Baohua
College of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang 712100, China.
Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Xianyang 712100, China.
Animals (Basel). 2021 Dec 1;11(12):3422. doi: 10.3390/ani11123422.
Mastitis is a common and important clinical disease in ruminants. This may be associated with inflammatory fibrosis if not treated promptly. Inflammation-derived fibrosis is usually accompanied by epithelial-mesenchymal transition (EMT) in epithelial cells. However, the precise molecular mechanism underlying mastitis-induced fibrosis remains unclear. Nuclear factor kappa-B (NF-κB) and Snail are key regulators of EMT. In this study, primary goat mammary epithelial cells (GMECs) were treated with 10 μg/mL lipopolysaccharide (LPS) for 14 d to mimic the in vivo mastitis environment. After LPS treatment, the GMECs underwent mesenchymal morphological transformation and expressed mesenchymal cell markers. Snail expression was induced by LPS and was inhibited by suppression of the TLR4/NF-κB signaling pathway. Snail knockdown alleviated LPS-induced EMT and altered the expression of inflammatory cytokines. Finally, we found that the expression of key molecules of the TLR4/NF-κB/Snail signaling pathway was increased in mastitis tissues. These results suggest that Snail plays a vital role in LPS-induced EMT in GMECs and that the mechanism is dependent on the activation of the TLR4/NF-κB signaling pathway.
乳腺炎是反刍动物常见且重要的临床疾病。若不及时治疗，可能会引发炎症性纤维化。炎症引发的纤维化通常伴随着上皮细胞的上皮-间质转化（EMT）。然而，乳腺炎诱导纤维化的确切分子机制仍不清楚。核因子κB（NF-κB）和Snail是EMT的关键调节因子。在本研究中，用10μg/mL脂多糖（LPS）处理原代山羊乳腺上皮细胞（GMECs）14天，以模拟体内乳腺炎环境。LPS处理后，GMECs发生间充质形态转化并表达间充质细胞标志物。Snail表达由LPS诱导，并通过抑制TLR4/NF-κB信号通路而被抑制。敲低Snail可减轻LPS诱导的EMT并改变炎性细胞因子的表达。最后，我们发现TLR4/NF-κB/Snail信号通路关键分子在乳腺炎组织中的表达增加。这些结果表明，Snail在LPS诱导的GMECs的EMT中起重要作用，其机制依赖于TLR4/NF-κB信号通路的激活。
