Approaching Biomarkers of Membranous Nephropathy from a Murine Model to Human Disease

Abstract

Background. Membranous glomerulonephropathy (MN) is the most prevalent cause of nephrotic syndrome in adult humans. However, the specific biomarkers of MN have not been fully elucidated. We examined the alterations in gene expression associated with the development of MN. Methods. Murine MN was induced by cationic bovine serum albumin (cBSA). After full-blown MN, cDNA microarray analysis was performed to identify gene expression changes, and highly expressed genes were evaluated as markers both in mice and human kidney samples. Results. MN mice revealed clinical proteinuria and the characteristic diffuse thickening of the glomerular basement membrane. There were 175 genes with significantly different expressions in the MN kidneys compared with the normal kidneys. Four genes, metallothionein-1 (Mt1), cathepsin D (CtsD), lymphocyte 6 antigen complex (Ly6), and laminin receptor-1 (Lamr1), were chosen and quantified. Mt1 was detected mainly in tubules, Lamr1 was highly expressed in glomeruli, and CtsD was detected both in tubules and glomeruli. The high expressions of Lamr1 and CtsD were also confirmed in human kidney biopsies. Conclusion. The murine MN model resembled the clinical and pathological features of human MN and may provide a tool for investigating MN. Applying cDNA microarray analysis may help to identify biomarkers for human MN.

Gene Expression Analysis and Urinary Biomarker Assays Reveal Activation of Tubulointerstitial Injury Pathways in a Rodent Model of Chronic Proteinuria (Doxorubicin Nephropathy)

“…Table 2 lists the 53 transcripts that have been previously reported to play a role in ischemia-reperfusion (IR), nephrotoxicity, or proteinuria [4,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45], suggesting a striking overlap in the kidney's transcriptional responses to a wide variety of insults. In the tubules, there was upregulation of many cell cycle, cell stress, apoptosis and inflammatory genes with concurrent downregulation of membrane transporters.…”

Urinary Xist is a potential biomarker for membranous nephropathy

“…Membranous nephropathy was induced as previously described [12,13]. Both control and experimental groups were immunized with 0.2 mg cationic bovine serum albumin (cBSA; Chondrex, Redmond, USA) emulsified in an equal volume of complete Freund's adjuvant (Sigma, St. Louis, USA).…”

Quantitative proteomic analysis of cyclosporine-induced toxicity in a human kidney cell line and comparison with tacrolimus

“…Cathepsin D has also been identified as a renin-like enzyme that catalyzes angiotensinogen cleavage to angiotensin-I. In kidneys, its expression is up-regulated in chronic progressive nephropathy, especially during chronic inhibition of nitric oxide synthesis in the kidney [52] and membranous glomerulonephropathy [53]. CsA and TAC were previously reported to inhibit nitric-oxide secretion in renal proximal tubule cells, thus potentiating CNIs-induced apoptosis [14].…”