Zhang Ling, Lin Yanwen, Xu Xinrui, Liu Huihui, Wang Xiangyu, Pan Jihong
Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences; Key Lab for Biotech-Drugs of National Health Commission, Ji'nan, Shandong, China.
Intractable Rare Dis Res. 2023 Feb;12(1):45-57. doi: 10.5582/irdr.2022.01121.
Rheumatoid arthritis (RA) is one of the most widespread chronic immune-mediated inflammatory diseases characterized by continuous erosion of bone and cartilage by synovial hyperplasia. Telotristat Etiprate is an inhibitor of tryptophan hydroxylase, a rate-limiting enzyme in the biosynthesis of serotonin. Telotristat Etiprate can be used in the treatment of carcinoid syndrome. The purpose of this study was to explore the effect of Telotristat Etiprate on RA and its mechanism. We investigated Telotristat Etiprate in collagen-induced arthritis (CIA) model mice and in rheumatoid arthritis synovial fibroblasts (RASFs). Results showed that Telotristat Etiprate had anti-inflammatory effects both and , can inhibit the invasion and migration of cells, inhibit the formation of pannus, and induce cell apoptosis. Transcriptome sequencing (RNA-seq) and mass spectrometry analysis showed that Galectins-3 (LGALS3) could be a newly identified target of Telotristat Etiprate, affecting the phosphorylation of the MAPK signaling pathway through UBE2L6, thereby improving RA.
类风湿性关节炎（RA）是最常见的慢性免疫介导的炎症性疾病之一，其特征是滑膜增生导致骨和软骨持续侵蚀。替洛曲汀是色氨酸羟化酶的抑制剂，色氨酸羟化酶是血清素生物合成中的限速酶。替洛曲汀可用于治疗类癌综合征。本研究的目的是探讨替洛曲汀对类风湿性关节炎的影响及其机制。我们在胶原诱导的关节炎（CIA）模型小鼠和类风湿性关节炎滑膜成纤维细胞（RASFs）中研究了替洛曲汀。结果表明，替洛曲汀具有抗炎作用，既能抑制细胞的侵袭和迁移，抑制血管翳的形成，又能诱导细胞凋亡。转录组测序（RNA-seq）和质谱分析表明，半乳糖凝集素-3（LGALS3）可能是替洛曲汀新发现的靶点，通过UBE2L6影响丝裂原活化蛋白激酶（MAPK）信号通路的磷酸化，从而改善类风湿性关节炎。
