MiR-214-3p may alleviate T-2 toxin-induced chondrocyte apoptosis and matrix degradation by regulating NF-KB signaling pathway in vitro

作者：Liu, Lele; Zhang, Hua; Jin, Baiming; Li, Haonan; Zheng, Xiujuan; Li, Xuying; Li, Mengyuan; Li, Mingqi; Nian, Shijing; Wang, Kewei^*

来源：Toxicon : official journal of the International Society on Toxinology , 2023, 225: 107049.

DOI：10.1016/j.toxicon.2023.107049

• miR-214-3p
• Chondrocyte
• T-2 toxin
• Apoptosis
• NF-kB

T-2 toxin is part of the most toxic fungal secondary metabolites contaminating different kinds of grains. Previous studies have demonstrated that T-2 toxin can influence the survival of chondrocytes and extracellular matrix (ECM) composition. MiR-214-3p is essential for the homeostasis of chondrocytes and ECM. However, the mo-lecular machinery underlying T-2 toxin-induced chondrocyte apoptosis and ECM degradation remain to be elucidated. The present study aimed to investigate the mechanism of miR-214-3p's involvement in T-2 toxin -induced chondrocyte apoptosis and ECM degradation. Meanwhile, the role of the NF-icB signaling pathway was scrutinized. C28/I2 chondrocytes were treated with 8 ng/ml of T-2 toxin for 24 h, after the pretreatment of miR-214-3p interfering RNAs for 6 h. Gene and protein levels involved in chondrocyte apoptosis and ECM degradation were assessed through RT-PCR and Western blotting. The apoptosis rate of chondrocyte was measured by flow cytometry. Results and data indicated that miR-214-3p was decreased in a dose-dependent manner at different concentrations of T-2 toxin. The enhancement of miR-214-3p could alleviate chondrocyte apoptosis and ECM degradation due to T-2 toxin exposure. The upregulation of miR-214-3p was associated with the decreased expression of apoptosis-promoting genes such as Bax and Cleaved-caspase3/caspase3 as well as the increased expression of anti-apoptotic genes such as Bcl2 and Survivin. Furthermore, miR-214-3p stimulated the relative protein expression of collagen II but inhibited the expression of MMP13. Overexpressing miR-214-3p could suppress the relative protein expression of IKKll and phospho-p65/p65, thus blocking the activation of the NF-icB signaling pathway. The study suggested that the miR-214-3p attenuates T-2 toxin-induced chon-drocyte apoptosis and ECM degradation through a potential NF-icB signaling pathway.

• 单位
  哈尔滨医科大学