4.7 Article

T Cells Mediate Kidney Tubular Injury via Impaired PDHA1 and Autophagy in Type 1 Diabetes

期刊

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 107, 期 9, 页码 2556-2570

出版社

ENDOCRINE SOC
DOI: 10.1210/clinem/dgac378

关键词

PDHA1; NGAL; Th 1 cells; kidney tubular injury; type 1 diabetes

资金

  1. China Medical University Hospital [DMR-107-053, DMR-107-055, DMR-108-040, DMR-110-063, DMR-110-112, DMR-110-209]
  2. Ministry of Science and Technology, Taiwan [MOST 106-2314-B-039-024-MY2, MOST 109-2314B-039-035]

向作者/读者索取更多资源

This study aimed to evaluate the role of PDHA1 in the regulation of tubular cells and CD4(+) T cells and further investigate their interaction in tubular cell injury in T1DM. The results revealed that Th1 cells induced tubular cell injury through dysregulated metabolic reprogramming and autophagy, providing a new therapeutic approach for kidney tubular injury in T1DM.
Context Nephropathy is a severe complication of type 1 diabetes (T1DM). However, the interaction between the PDHA1-regulated mechanism and CD4(+ )T cells in the early stage of kidney tubular injury remains unknown. Objective To evaluate the role of PDHA1 in the regulation of tubular cells and CD4(+ )T cells and further to study its interaction in tubular cell injury in T1DM. Methods Plasma and total RNA were collected from T cells of T1DM patients (n = 35) and healthy donors (n = 33) and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, PDHA1, and biomarkers of CD4(+ )T cells including T helper 1 cells (Th1) and regulatory T cells (Treg) markers. HK-2 cells cocultured with CD4(+ )T cells from T1DM patients or healthy donors (HDs) to evaluate the interaction with CD4(+ )T cells. Results Increased PDHA1 gene expression levels in CD4(+ )T cells were positively associated with the plasma level of NGAL in T1DM patients and HDs. Our data demonstrated that the Th1/Treg subsets skewed Th1 in T1DM. Knockdown of PDHA1 in kidney tubular cells decreased ATP/ROS production, NAD/NADH ratio, mitochondrial respiration, and cell apoptosis. Furthermore, PDHA1 depletion induced impaired autophagic flux. Coculture of tubular cells and T1DM T cells showed impaired CPT1A, upregulated FASN, and induced kidney injury. Conclusion Our findings indicate that Th1 cells induced tubular cell injury through dysregulated metabolic reprogramming and autophagy, thereby indicating a new therapeutic approach for kidney tubular injury in T1DM.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据