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Claudin-1 作为一个在肥胖中诱导的新型靶基因,与炎症、纤维化和细胞分化相关。

Claudin-1 as a novel target gene induced in obesity and associated to inflammation, fibrosis, and cell differentiation.

机构信息

Department of Basic Health Sciences, Campus Alcorcón, University Rey Juan Carlos (URJC), Madrid E-28922, Spain.

Endocrinology Department, Fundació Institut Germans Trias i Pujol, Barcelona 08916, Spain.

出版信息

Eur J Endocrinol. 2024 Mar 2;190(3):201-210. doi: 10.1093/ejendo/lvae018.

DOI:10.1093/ejendo/lvae018
PMID:38375549
Abstract

OBJECTIVE

T lymphocytes from visceral and subcutaneous white adipose tissues (vWAT and sWAT, respectively) can have opposing roles in the systemic metabolic changes associated with obesity. However, few studies have focused on this subject. Claudin-1 (CLDN1) is a protein involved canonically in tight junctions and tissue paracellular permeability. We evaluated T-lymphocyte gene expression in vWAT and sWAT and in the whole adipose depots in human samples.

METHODS

A Clariom D-based transcriptomic analysis was performed on T lymphocytes magnetically separated from vWAT and sWAT from patients with obesity (Cohort 1; N = 11). Expression of candidate genes resulting from that analysis was determined in whole WAT from individuals with and without obesity (Cohort 2; patients with obesity: N = 13; patients without obesity: N = 14).

RESULTS

We observed transcriptional differences between T lymphocytes from sWAT compared with vWAT. Specifically, CLDN1 expression was found to be dramatically induced in vWAT T cells relative to those isolated from sWAT in patients with obesity. CLDN1 was also induced in obesity in vWAT and its expression correlates with genes involved in inflammation, fibrosis, and adipogenesis.

CONCLUSION

These results suggest that CLDN1 is a novel marker induced in obesity and differentially expressed in T lymphocytes infiltrated in human vWAT as compared with sWAT. This protein may have a crucial role in the crosstalk between T lymphocytes and other adipose tissue cells and may contribute to inflammation, fibrosis, and alter homeostasis and promote metabolic disease in obesity.

摘要

目的

内脏和皮下白色脂肪组织(分别为 vWAT 和 sWAT)中的 T 淋巴细胞在与肥胖相关的全身代谢变化中可能具有相反的作用。然而,很少有研究关注这个问题。 Claudin-1(CLDN1)是一种参与紧密连接和组织旁细胞通透性的经典蛋白。我们评估了人类样本中 vWAT 和 sWAT 中的 T 淋巴细胞和整个脂肪组织中的基因表达。

方法

对从肥胖患者的 vWAT 和 sWAT 中分离的 T 淋巴细胞进行了基于 Clariom D 的转录组分析(队列 1;N = 11)。在有和没有肥胖的个体的整个 WAT 中确定了该分析产生的候选基因的表达(队列 2;肥胖患者:N = 13;无肥胖患者:N = 14)。

结果

我们观察到 sWAT 中的 T 淋巴细胞与 vWAT 中的 T 淋巴细胞之间存在转录差异。具体来说,与从 sWAT 中分离的 T 细胞相比,肥胖患者 vWAT 中的 T 细胞中 CLDN1 的表达被显著诱导。CLDN1 在肥胖患者的 vWAT 中也被诱导,其表达与参与炎症、纤维化和脂肪生成的基因相关。

结论

这些结果表明,CLDN1 是一种在肥胖中诱导的新型标志物,在与 sWAT 相比,在浸润人 vWAT 的 T 淋巴细胞中差异表达。这种蛋白质在 T 淋巴细胞与其他脂肪组织细胞之间的串扰中可能具有关键作用,并可能导致炎症、纤维化和改变稳态,促进肥胖中的代谢疾病。

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