Proteomic Analysis of the Intestinal Resistance to Thyroid Hormone Mouse Model With Thyroid Hormone Receptor Alpha Mutations.
Proteomic Analysis of the Intestinal Resistance to Thyroid Hormone Mouse Model With Thyroid Hormone Receptor Alpha Mutations.
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DOI：
10.3389/fendo.2022.773516
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发表时间：
2022
影响因子：
5.2
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中科院分区：
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甲状腺激素在脊椎动物的发育过程中至关重要，影响许多器官和组织的功能，尤其是肠道。三碘甲状腺原氨酸（T3）是活性形式，可以与甲状腺激素核受体（TR）结合，在脊椎动物的发育中发挥至关重要的作用。 Thra E403X 突变模仿了患者对甲状腺激素 α 的抵抗力。为了研究 TRα1 对肠道发育影响的机制，本研究采用蛋白质组学分析来鉴定纯合子 Thra E403X/E403X 和野生型 Thra +/+ 小鼠回肠远端的差异表达蛋白 (DEP)。总共鉴定出 1,189 个 DEP，其中包括 603 个上调蛋白和 586 个下调蛋白。蛋白质组学分析表明，DEPs在代谢过程、发育过程、营养物质转运和肠道免疫系统相关途径中高度富集。在这些 DEP 中，有 20 种蛋白质通过平行反应监测分析得到了验证。我们的肠道蛋白质组学结果为未来的研究提供了有希望的候选者，因为它们提出了 TRα1 可能影响肠道发育的新机制，例如肠道营养物质的运输以及肠道先天性和适应性免疫屏障的建立。
Thyroid hormone is critical during the development of vertebrates and affects the function of many organs and tissues, especially the intestine. Triiodothyronine (T3) is the active form and can bind to thyroid hormone nuclear receptors (TRs) to play a vital role in the development of vertebrates. The resistance to thyroid hormone α, as seen in patients, has been mimicked by the Thra E403X mutation. To investigate the mechanisms underlying the effect of TRα1 on intestinal development, the present study employed proteomic analysis to identify differentially expressed proteins (DEPs) in the distal ileum between homozygous Thra E403X/E403X and wild-type Thra +/+ mice. A total of 1,189 DEPs were identified, including 603 upregulated and 586 downregulated proteins. Proteomic analysis revealed that the DEPs were highly enriched in the metabolic process, the developmental process, the transporter of the nutrients, and the intestinal immune system-related pathway. Of these DEPs, 20 proteins were validated by parallel reaction monitoring analysis. Our intestinal proteomic results provide promising candidates for future studies, as they suggest novel mechanisms by which TRα1 may influence intestinal development, such as the transport of intestinal nutrients and the establishment of innate and adaptive immune barriers of the intestine.