Complement 7 Is Up-Regulated in Human Early Diabetic Kidney Disease
| Autor: | Monica Sircar, Isaac E. Stillman, S. Ananth Karumanchi, Ravi Thadhani, Towia A. Libermann, Zsuzsanna K. Zsengellér, Martin K. Selig, Ivy A. Rosales, Dihua Xu |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Genetic Markers Male 0301 basic medicine Candidate gene Adolescent 030232 urology & nephrology Kidney Article Pathology and Forensic Medicine Transcriptome Andrology Diabetic nephropathy Young Adult 03 medical and health sciences 0302 clinical medicine Diabetes mellitus Humans Medicine Diabetic Nephropathies Renal Insufficiency Chronic Aged business.industry Kidney metabolism Middle Aged medicine.disease Complement C7 Up-Regulation Complement system Early Diagnosis 030104 developmental biology medicine.anatomical_structure Female business Kidney disease |
| Zdroj: | The American Journal of Pathology. 188:2147-2154 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2018.06.018 |
| Popis: | There is a temporal window from the time diabetes is diagnosed to the appearance of overt kidney disease during which time the disease progresses quietly without detection. Currently, there is no way to detect early diabetic nephropathy (EDN). Herein, we performed an unbiased assessment of gene-expression analysis of postmortem human kidneys to identify candidate genes that may contribute to EDN. We then studied one of the most promising differentially expressed genes in both kidney tissue and blood samples. Differential transcriptome analysis of EDN kidneys and matched nondiabetic controls showed alterations in five canonical pathways, and among them the complement pathway was the most significantly altered. One specific complement pathway gene, complement 7 (C7), was significantly elevated in EDN kidney. Real-time PCR confirmed more than a twofold increase of C7 expression in EDN kidneys compared with controls. Changes in C7 gene product level were confirmed by immunohistochemistry. C7 protein levels were elevated in proximal tubules of EDN kidneys. Serum C7 protein levels were also measured in EDN and control donors. C7 levels were significantly higher in EDN serum than control serum. This latter finding was independently confirmed in a second set of blood samples from a previously collected data set. Together, our data suggest that C7 is associated with EDN, and can be used as a molecular target for detection and/or treatment of EDN. |
| Databáze: | OpenAIRE |
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