Xu De Lai, Pan Jie
Department of Pharmacy, the Second Affiliated Hospital of Soochow University, No 1055, Sanxiang Road, Gusu District, Suzhou, 215004 Jiangsu China.
3 Biotech. 2021 Apr;11(4):162. doi: 10.1007/s13205-021-02710-1. Epub 2021 Mar 9.
This study investigated the effect of autophagy-related gene transcription factor EB (TFEB) on the rheumatoid arthritis (RA) and explored whether TFEB regulated RA by autophagy. The Sprague-Dawley rats were divided into two groups ( = 6). The rats were stimulated with the mixture of the type II collagen and Freund's adjuvant or PBS at the root of the tail. Results showed that swollen and deformed joints were discovered, the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were elevated, and hematoxylin and eosin staining showed the inflammatory cells infiltrate the synovial tissue in the RA rats, compared to the control group. Immunohistochemistry displayed that the expressions of TFEB and LC3B increased in the synovial tissues of RA rats, whereas p62 decreased. The silence of TFEB in the RA-fibroblast-like synoviocytes (RA-FLS) decreased the protein expressions of LC3B, compared to the siRNA NC group. Meanwhile, the activity of FLS was raised, whereas the levels of TNF-α and IL-6 decreased in RA-FLS with TFEB knockdown. In conclusion, our study revealed that TFEB plays a crucial role in the progress of RA by regulating autophagy, which might provide novel targets for the therapy of RA.
本研究探讨自噬相关基因转录因子EB（TFEB）对类风湿关节炎（RA）的影响，并探究TFEB是否通过自噬调节RA。将Sprague-Dawley大鼠分为两组（每组n = 6）。在大鼠尾根部用II型胶原蛋白和弗氏佐剂混合物或PBS进行刺激。结果显示，与对照组相比，RA大鼠出现关节肿胀和畸形，肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平升高，苏木精-伊红染色显示炎性细胞浸润滑膜组织。免疫组化显示，RA大鼠滑膜组织中TFEB和LC3B的表达增加，而p62减少。与siRNA NC组相比，RA成纤维样滑膜细胞（RA-FLS）中TFEB沉默降低了LC3B的蛋白表达。同时，TFEB敲低的RA-FLS中FLS活性升高，而TNF-α和IL-6水平降低。总之，我们的研究表明TFEB通过调节自噬在RA进展中起关键作用，这可能为RA治疗提供新的靶点。
