类风湿关节炎中SLC2A3的功能特性：揭示其在铁死亡和炎症途径中的作用

Functional Characterization of SLC2A3 in Rheumatoid Arthritis: Unraveling Its Role in Ferroptosis and Inflammatory Pathways.

作者信息

Lin Zhiping, Li Peng, Wang Chaojun, Tan Hongchang

机构信息

Department of Joint Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

出版信息

Int J Rheum Dis. 2024 Dec;27(12):e70009. doi: 10.1111/1756-185X.70009.

DOI:10.1111/1756-185X.70009

PMID:39668736

Abstract

BACKGROUND

Hence, we investigated that the function and effects of SLC2A3 in rheumatoid arthritis (RA) and the underlying mechanism.

METHODS

C57BL/6 mice were immunized with bovine type II collagen to induce mice model of RA.

RESULTS

The expression of serum SLC2A3 was down-regulated, and was negative correlation with CRP, RF or anti-CCP in patients with RA. In mice model of RA, SLC2A3 mRNA and protein expression in joint tissue were reduced. Sh-SLC2A3 promoted RA and inflammation in mice model. SLC2A3 promoted cell growth and osteogenic differentiation of MC3T3-E1 cells in vitro model of RA. SLC2A3 reduced ferroptosis in vitro model or mice model of RA. SLC2A3 induced Tiam1 protein expression, and SLC2A3 protein linked with Tiam1 protein in model of RA. Tiam1 reduced the effects of sh-SLC2A3 on RA and inflammation in mice model. Tiam1 inhibitor the effects of SLC2A3 on osteogenic differentiation and ferroptosis in vitro model of RA.

CONCLUSIONS

Collectively, SLC2A3 reduced inflammation levels and ferroptosis through the inactivation of mitochondrial damage by Tiam1 in model of RA, could serve as a potent therapeutic agent for alleviating RA.

摘要

背景

因此，我们研究了溶质载体家族2成员3（SLC2A3）在类风湿关节炎（RA）中的功能、作用及其潜在机制。

方法

用牛II型胶原免疫C57BL/6小鼠以诱导RA小鼠模型。

结果

RA患者血清SLC2A3表达下调，且与CRP、RF或抗CCP呈负相关。在RA小鼠模型中，关节组织中SLC2A3 mRNA和蛋白表达降低。sh-SLC2A3促进RA小鼠模型的炎症反应。在RA体外模型中，SLC2A3促进MC3T3-E1细胞的生长和成骨分化。SLC2A3在RA体外模型或小鼠模型中减少铁死亡。SLC2A3诱导Tiam1蛋白表达，且在RA模型中SLC2A3蛋白与Tiam1蛋白相连。Tiam1减轻sh-SLC2A3对RA小鼠模型炎症的影响。Tiam1抑制剂在RA体外模型中抑制SLC2A3对成骨分化和铁死亡的作用。