硒蛋白脱碘酶的生物学功能及其在骨性关节炎患者中的表达

doi:10.24920/003991

摘要/Abstract

摘要：

目的骨关节炎（osteoarthritis,OA）是一种常见的关节疾病,老年人尤其高发。碘甲状腺原氨酸脱碘酶（iodothyronine deiodinases,DIOs）作为一种重要的硒蛋白,在骨和关节疾病中发挥着关键作用。本研究旨在利用生物信息学方法探讨DIOs在OA发病机制中的作用。
方法通过对NCBI的GEO数据库中与OA相关的芯片数据进行数据挖掘,利用GenCLip 3.0,DAVID,STRING,Cytoscape和Network Analyst等工具分析DIOs的生物学功能,并用Review Manager5.3对数据进行Meta分析,研究DIOs在正常人和骨性关节炎患者中的表达。
结果聚类分析显示：DIOs的功能与甲状腺激素受体和碘甲状腺原氨酸有关。GO分析显示：DIOs主要参与乙醇代谢和含酚化合物代谢等生物过程,还与外源生物的细胞色素P450代谢和甲状腺激素信号传导有关。SULT1A1是PPI网络的核心节点。miRNAs和甲状腺激素与DIO1和DIO2存在交互作用。Meta分析显示：DIO3的表达在OA患者中显著上调（P <0.05）。
结论 DIOs的主要生物学功能与甲状腺激素的调节密切相关,而DIO3的上调表达可能在OA的发生中发挥关键作用。

关键词: 硒蛋白, 碘甲状腺原氨酸脱碘酶, 骨关节炎

Abstract:

Objective Iodothyronine deiodinases (DIOs) are important selenoproteins that play a key role in the bone and joint diseases. Osteoarthritis (OA) is the most prevalent joint disease especially in elders. This bioinformatic analysis was performed to explore the role of DIOs in OA pathogenesis.
Methods The biological functions of selenoprotein DIOs were analyzed by bioinformatic techniques, including GenCLip 3.0, Database for Annotation, Visualization and Integrated Discovery (DAVID), STRING, Cytoscape, and Network Analyst. The expression of DIOs in the healthy individuals and OA patients was determined by mining OA-related microarray data in the gene expression omnibus (GEO) database of National Center for Biotechnology Information and performing a Meta-analysis of the data with Review Manager 5.3.
Results Cluster analysis revealed that the function of the DIOs was associated with thyroid hormone receptor and iodothyronine; GO analysis showed that DIOs were mainly involved in biological processes, such as ethanol metabolism and phenol-containing compound metabolism and primarily involved in the cytochrome P450 metabolism of exogenous organisms and thyroid hormone signaling; SULT1A1 was the core node of the PPI network; miRNAs and thyroid hormones had some iterations with DIO1and DIO2; Meta-analysis showed that DIO3 expression was significantly up-regulated in OA patients (SMD = 0.31, 95%CI: 0.03, 0.59, P = 0.03).
Conclusions The main biological functions of DIOs were closely associated with the regulation of thyroid hormone. And the up-regulated expression of DIO3 may have crucial impact on the occurrence of OA.

Key words: selenoprotein, iodothyronine deiodinase, osteoarthritis

Xiaomei Ren, Li Zhang, Bao Xin, Qiling Liu, Wenwen Qian, Rongqiang Zhang. Biological Functions of Selenoprotein Iodothyronine Deiodinase and its Expression in Osteoarthritis[J].Chinese Medical Sciences Journal, 2022, 37(2): 142-150.

图/表 8

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Category	GO term ID	Biological function	Gene number	FDR value
BP	GO:0006067	Ethanol metabolism process	5	3.30×10^-9
	GO:0018958	Phenol-containing compound metabolic process	6	4.10×10^-9
	GO:1901615	Organic hydroxy compound metabolic process	8	1.79×10^-8
	GO:0051923	Sulfation	4	1.32×10^-7
	GO:0050427	3’-phosphoadenosine 5’-phosphosulfate metabolic process	4	3.72×10^-7
	GO:0006590	Thyroid hormone generation	3	8.60×10^-6
MF	GO:0004062	Aryl sulfotransferase activity	4	1.27×10^-8
	GO:0004800	Thyroxine 5’-deiodinase activity	3	1.37×10^-7
	GO:0047894	Flavonol 3-sulfotransferase activity	2	4.88×10^-5
	GO:0004024	Alcohol dehydrogenase activity, zinc-dependent	2	1.10×10^-4
	GO:0008430	Selenium binding	2	1.30×10^-4
	GO:0003824	Catalytic activity	11	3.00×10^-4
KEGG pathway	hsa05204	Chemical carcinogenesis	6	1.65×10^-10
	hsa00830	Retinol metabolism	4	9.05×10^-7
	hsa00980	Metabolism of xenobiotics by cytochrome P450	4	9.05×10^-7
	hsa00982	Drug metabolism by cytochrome P450	4	9.05×10^-7
	hsa04919	Thyroid hormone signaling pathway	3	2.60×10^-4
	hsa00053	Ascorbate and aldarate metabolism	2	6.00×10^-4

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