Identification of cathepsin L as a potential sex-specific biomarker for renal damage

ABSTRACT: The renin-angiotensin system is a well-known regulator of blood pressure and plays an important role in the pathogenesis of cardiovascular disease and renal damage. Genetic factors, including single nucleotide polymorphisms and sex, are increasingly recognized as potential risk factors for the development of cardiovascular disease. Double transgenic rats (dTGR), harboring human renin and angiotensinogen genes, were used in this study to investigate potential sex differences influencing renal function and renal gene expression. dTGR males and females had comparable increases in blood pressure, whereas body weight, albuminuria/proteinuria and urine flow rate were higher in males. At eight weeks of age renal plasma flow and glomerular filtration rate were proportionally lower in males, and renal vascular resistance tended to be higher. Males developed more severe tubulointerstitial and vascular lesions. By the end of week eight, 40% of the males, but none of the females had died. Genome expression studies were performed with RNA from kidneys of 7-week-old male and female dTGR and control rats to further investigate the sex-related differences on a molecular level. Forty-five genes showed sex-dependent expression patterns in dTGR that were significantly different compared to controls. Cathepsin L, one of the genes differentially expressed between the sexes, was shown to be also strongly associated with the degree of renal injury. In dTGR, urinary CTSL at week 7 was higher in males (ng/24 hours: M 512 +/- 163, F 132 +/- 70). These results reveal a potential new biomarker for the personalized diagnosis and management of chronic kidney disease.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE19058 | GEO | 2011/01/25

SECONDARY ACCESSION(S): PRJNA120561

REPOSITORIES: GEO