Telotristat Etiprate alleviates rheumatoid arthritis by targeting LGALS3 and affecting MAPK signaling.

IF 1.1 Q2 MEDICINE, GENERAL & INTERNAL
Ling Zhang, Yanwen Lin, Xinrui Xu, Huihui Liu, Xiangyu Wang, Jihong Pan
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引用次数: 2

Abstract

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 in vitro and in vivo, 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.

Telotristat Etiprate通过靶向LGALS3和影响MAPK信号通路缓解类风湿关节炎。
类风湿性关节炎(RA)是一种最普遍的慢性免疫介导的炎症性疾病,其特征是滑膜增生引起的骨和软骨的持续侵蚀。Telotristat Etiprate是色氨酸羟化酶的抑制剂,色氨酸羟化酶是5 -羟色胺生物合成中的限速酶。特立司他可用于治疗类癌综合征。本研究旨在探讨特立司他对类风湿关节炎的作用及其机制。我们在胶原诱导的关节炎(CIA)模型小鼠和类风湿关节炎滑膜成纤维细胞(rasf)中研究了特立司他酯。结果表明,特立司他在体外和体内均具有抗炎作用,能抑制细胞的侵袭和迁移,抑制肠膜的形成,诱导细胞凋亡。转录组测序(RNA-seq)和质谱分析显示,galectin -3 (LGALS3)可能是Telotristat Etiprate新发现的靶点,通过UBE2L6影响MAPK信号通路的磷酸化,从而改善RA。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Intractable & rare diseases research
Intractable & rare diseases research MEDICINE, GENERAL & INTERNAL-
CiteScore
2.10
自引率
0.00%
发文量
29
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