Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China, Ningxia University, Yinchuan 750021, China.
Int J Mol Sci. 2023 Sep 25;24(19):14520. doi: 10.3390/ijms241914520.
Pore-forming toxins (PFTs) exert physiological effects by rearrangement of the host cell cytoskeleton. -secreted PFTs play an important role in bovine mastitis. In the study, we examined the effects of recombinant Panton-Valentine leukocidin (rPVL) on cytoskeleton rearrangement, and identified the signaling pathways involved in regulating the process in bovine mammary epithelial cells (BMECs) in vitro. Meanwhile, the underlying regulatory mechanism of baicalin for this process was investigated. The results showed that . induced cytoskeleton rearrangement in BMECs mainly through PVL. . and rPVL caused alterations in the cell morphology and layer integrity due to microfilament and microtubule rearrangement and focal contact inability. rPVL strongly induced the phosphorylation of cofilin at Ser3 mediating by the activation of the RhoA/ROCK/LIMK pathway, and resulted in the activation of loss of actin stress fibers, or the hyperphosphorylation of Tau at Ser396 inducing by the inhibition of the PI3K/AKT/GSK-3β pathways, and decreased the microtubule assembly. Baicalin significantly attenuated rPVL-stimulated cytoskeleton rearrangement in BMECs. Baicalin inhibited cofilin phosphorylation or Tau hyperphosphorylation via regulating the activation of RhoA/ROCK/LIMK and PI3K/AKT/GSK-3β signaling pathways. These findings provide new insights into the pathogenesis and potential treatment in . causing bovine mastitis.
孔形成毒素 (PFTs) 通过重排宿主细胞细胞骨架发挥生理作用。-分泌的 PFTs 在牛乳腺炎中发挥重要作用。在研究中，我们研究了重组潘顿-瓦伦丁白细胞毒素 (rPVL) 对细胞骨架重排的影响，并鉴定了体外牛乳腺上皮细胞 (BMECs) 中调节该过程的信号通路。同时，研究了黄芩苷对此过程的潜在调节机制。结果表明，rPVL 通过 PVL 主要诱导 BMECs 中的细胞骨架重排。rPVL 和 rPVL 导致细胞形态和层完整性改变，原因是微丝和微管重排以及焦点接触丧失。rPVL 强烈诱导 cofilin 在丝氨酸 3 位磷酸化，通过 RhoA/ROCK/LIMK 途径的激活介导，导致肌动蛋白应力纤维丧失活性，或通过 PI3K/AKT/GSK-3β 途径的抑制导致 Tau 在丝氨酸 396 位过度磷酸化，导致微管组装减少。黄芩苷显著减弱 rPVL 刺激的 BMECs 细胞骨架重排。黄芩苷通过调节 RhoA/ROCK/LIMK 和 PI3K/AKT/GSK-3β 信号通路的激活来抑制 cofilin 磷酸化或 Tau 过度磷酸化。这些发现为 rPVL 引起牛乳腺炎的发病机制和潜在治疗提供了新的见解。
