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http://purl.uniprot.org/citations/35731579http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/35731579http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/35731579http://purl.org/dc/terms/identifier"doi:10.1210/clinem/dgac378"xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/author"Huang C.Y."xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/author"Lin Y.J."xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/author"Liu S.C."xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/author"Hsieh C.H."xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/author"Wang C.H."xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/author"Chiang S.L."xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/author"Tsai F.J."xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/author"Su P.H."xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/author"Huang Y.N."xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/author"Lu W.L."xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/author"Tsai T.H."xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/name"J Clin Endocrinol Metab"xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/pages"2556-2570"xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/title"T Cells Mediate Kidney Tubular Injury via Impaired PDHA1 and Autophagy in Type 1 Diabetes."xsd:string
http://purl.uniprot.org/citations/35731579http://purl.uniprot.org/core/volume"107"xsd:string
http://purl.uniprot.org/citations/35731579http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/35731579
http://purl.uniprot.org/citations/35731579http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/35731579
http://purl.uniprot.org/uniprot/#_A5YPB6-mappedCitation-35731579http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35731579
http://purl.uniprot.org/uniprot/#_P78557-mappedCitation-35731579http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35731579
http://purl.uniprot.org/uniprot/#_Q53GE3-mappedCitation-35731579http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35731579
http://purl.uniprot.org/uniprot/#_P08559-mappedCitation-35731579http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35731579
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