Complement 7 Is Up-Regulated in Human Early Diabetic Kidney Disease

Abstract

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 geneexpression 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.

PTGER3 and MMP-2 play potential roles in diabetic nephropathy via competing endogenous RNA mechanisms

“…The pathophysiology leading to DN and resultant renal failure from DM consists of hypertension, altered composition and proliferation, and sclerosis in glomerular [ 10 ]. Accordingly, the estimated glomerular filtration rate (eGFR), albuminuria, and hypertension are the clinical manifestations of DN [ 3 ]. However, the clinical usage of them could not make an accurate and definite diagnosis of DN and the degree of kidney damage [ 3 ].…”

Transcriptome Signatures Reveal Candidate Key Genes in the Peripheral Blood Mononuclear Cells of Patients With Coronary Artery Disease

“…Enriched genes such as noggin (NOG) [112], very low density lipoprotein receptor (VLDLR) [113] and AQP10 [114] were responsible for progression of obesity, but these genes may be involved in development of CAD. Enriched genes such as TRPM5 [115], crystallin, alpha A (CRYAA) [116], PAX6 [117], SORBS1 [118], SLC38A1 [119], complement component 7 (C7) [120] and PAX8 [121] were linked with advancement of diabetes, but these genes may be associated with pathogenesis of CAD. Enriched genes such as KCNJ11 [122], PKD2L1 [123], CSMD1 [124], SLC6A2 [125] and ATP2B3 [126] were liable for advancement of hypertension, but these genes may be involved in progression CAD.…”

Diabetic kidney diseases revisited: A new perspective for a new era

“…Specifically, a typical function of linking the top-down approach to translational DKD research is biomarker identification, especially for the diagnosis of incipient DKD. As presented in Table 2, several well-known biomarkers such as Kidney Injury Molecule 1 (KIM-1), Neutrophil Gelatinase-Associated Lipocalin (NGAL), Monocyte Chemoattractant Protein-1 (MCP-1), Epidermal Growth Factor (EGF), N-acetyl-β- d -glucosaminidase (NAG), β2-microglobulin, Complement 7, IgG4, and Smad1 have already been identified as early signals of DKD by traditional experimental methods in various clinical cohorts studies over the past years [[141], [142], [143], [144], [145], [146], [147], [148], [149]]. However, few of these biomarkers have been truly implemented in the clinic so far because the specificity and sensitivity of most of these biomarkers lack rigorous external clinical validation.…”