Yan Shuping, Xie Nana, Aleem Muhammad Tahir, Ji Xiaoxia, Zhang Chonghao, Cao Xiyue, Zhang Yuanshu
Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Vet Microbiol. 2022 May;268:109398. doi: 10.1016/j.vetmic.2022.109398. Epub 2022 Mar 19.
Streptococcus uberis (S. uberis) is an environmentally important pathogenic bacterium and is the main pathogenic microorganism responsible for mastitis, which causes significant economic losses worldwide. Currently, there is no particularly effective treatment other than antibiotic therapy. Angiotensin-converting enzyme 2 (ACE2) plays an anti-inflammatory as well as an anti-injury role in numerous inflammatory diseases. Therefore, this study aimed to assess the hypothesis that S. uberis-induced mammary epithelial cells injury associated with ACE2, angiotensin II (Ang II) as well as angiotensin 1-7 (Ang-(1-7)) imbalance and that overexpression of ACE2 can repair S. uberis-induced mammary epithelial cells injury. We observed that the expression level of ACE2 was significantly downregulated after treatment of EpH4-Ev cells with S. uberis. Next, this assay verified the role of ACE2 in S. uberis-induced inflammatory injury in EpH4-Ev cells by overexpressing the ACE2 gene as well as its silencing. The results showed that overexpression of the ACE2 gene significantly activated the interleukin-10/signal transducer and activator of transcription 3/suppressors-of-cytokine-signaling 3 (IL-10/STAT3/SOCS3) pathway, thereby inhibiting the nuclear factor-κB (NF-κB) as well as pyroptosis pathways. Furthermore, overexpression of the ACE2 gene reversed the downregulation of zonula occludens 1 (ZO-1), Occludin, Claudin-1, and Claudin-2 caused by S. uberis, suggesting that ACE2 could promote to repair the blood-milk barrier. However, siRNA silencing of the ACE2 gene produced the opposite effect. These results suggest that ACE2 ameliorates S. uberis-induced mammary epithelial cells injury. AVAILABILITY OF DATA: All data generated or analyzed during this study are included within the article and its additional information file.
乳房链球菌是一种对环境具有重要影响的病原菌，是导致乳腺炎的主要致病微生物，在全球范围内造成了重大经济损失。目前，除抗生素治疗外，没有特别有效的治疗方法。血管紧张素转换酶2（ACE2）在多种炎症性疾病中发挥抗炎和抗损伤作用。因此，本研究旨在评估以下假设：乳房链球菌诱导的乳腺上皮细胞损伤与ACE2、血管紧张素II（Ang II）以及血管紧张素1-7（Ang-(1-7)）失衡有关，且ACE2的过表达可以修复乳房链球菌诱导的乳腺上皮细胞损伤。我们观察到，用乳房链球菌处理EpH4-Ev细胞后，ACE2的表达水平显著下调。接下来，本试验通过过表达ACE2基因及其沉默来验证ACE2在乳房链球菌诱导的EpH4-Ev细胞炎症损伤中的作用。结果表明，ACE2基因的过表达显著激活了白细胞介素-10/信号转导和转录激活因子3/细胞因子信号抑制因子3（IL-10/STAT3/SOCS3）通路，从而抑制了核因子-κB（NF-κB）以及焦亡通路。此外，ACE2基因的过表达逆转了由乳房链球菌引起的紧密连接蛋白1（ZO-1）、闭合蛋白、紧密连接蛋白-1和紧密连接蛋白-2的下调，表明ACE2可以促进血乳屏障的修复。然而，ACE2基因的siRNA沉默产生了相反的效果。这些结果表明，ACE2可改善乳房链球菌诱导的乳腺上皮细胞损伤。数据可用性：本研究期间生成或分析的所有数据均包含在文章及其附加信息文件中。
