YAP 在 T-2 毒素诱导的软骨细胞增殖和基质降解抑制中发挥保护作用。
YAP plays a protective role in T-2 toxin-induced inhibition of chondrocyte proliferation and matrix degradation.
机构信息
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, 150081, China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin, 150081, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health，; Harbin Medical University, Harbin, 150081, China; Institute of Cell Biotechnology, China and Russia Medical Research Center, Harbin Medical University, Harbin, 150081, China.
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, 150081, China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin, 150081, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health，; Harbin Medical University, Harbin, 150081, China; Institute of Cell Biotechnology, China and Russia Medical Research Center, Harbin Medical University, Harbin, 150081, China; Department of Preventive Medicine, Qiqihar Medical University, Qiqihar, 161006, China.
出版信息
Toxicon. 2022 Aug;215:49-56. doi: 10.1016/j.toxicon.2022.06.005. Epub 2022 Jun 10.
Previous research has shown that T-2 toxin can damage cartilage, resulting in a disease phenotype similar to osteoarthritis. The precise molecular mechanism by which T-2 toxin causes chondrocyte injury, however, is unknown. The purpose of this study was to look into the role of YAP in T-2 toxin-induced rat chondrocyte injury. Based on research results, T-2 toxin decreased the levels of collagen II and PCNA while increasing the expression of matrix metalloproteinase MMP13. These findings supported the T-2 toxin's detrimental effect on chondrocytes. YAP's role in T-2 toxin-induced chondrocyte injury was also investigated. Total YAP and related nuclear proteins were found to decrease as the concentration of T-2 toxin increased. While PYAP expression was not significantly altered in response to T-2 toxin, the PYAP/YAP ratio decreased as the T-2 toxin concentration increased, implying that the HIPPO signaling pathway was activated. Furthermore, the YAP-specific inhibitor Verteporfin was used to investigate the role of YAP in T-2 toxin-induced chondrocyte injury. YAP inhibition increased MMP13 expression while decreasing COL2 and PCNA levels. In summary, the current study found that T-2 toxin decreased the levels of COL2 and PCNA while increasing the expression of MMP13 in chondrocytes after inhibiting YAP, providing a new insight into the mechanism of T-2 toxin-induced cartilage damage.
先前的研究表明，T-2 毒素可损伤软骨，导致类似骨关节炎的疾病表型。然而，T-2 毒素引起软骨细胞损伤的确切分子机制尚不清楚。本研究旨在探讨 YAP 在 T-2 毒素诱导的大鼠软骨细胞损伤中的作用。研究结果表明，T-2 毒素降低了 II 型胶原和 PCNA 的水平，同时增加了基质金属蛋白酶 MMP13 的表达。这些发现支持 T-2 毒素对软骨细胞的有害作用。还研究了 YAP 在 T-2 毒素诱导的软骨细胞损伤中的作用。随着 T-2 毒素浓度的增加，总 YAP 和相关核蛋白的表达减少。虽然 T-2 毒素对 PYAP 的表达没有显著影响，但随着 T-2 毒素浓度的增加，PYAP/YAP 比值降低，表明 HIPPO 信号通路被激活。此外，还使用 YAP 特异性抑制剂 Verteporfin 来研究 YAP 在 T-2 毒素诱导的软骨细胞损伤中的作用。YAP 抑制增加了 MMP13 的表达，同时降低了 COL2 和 PCNA 的水平。总之，本研究发现，T-2 毒素抑制 YAP 后降低了软骨细胞中 COL2 和 PCNA 的水平，同时增加了 MMP13 的表达，为 T-2 毒素诱导的软骨损伤机制提供了新的见解。
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