Immunohistochemistry of kidney and mesenteric...

Immunohistochemistry of kidney and mesenteric tissues of heterozygous Pkd2 knock out mice as an investigatory tool for detecting endothelial dysfunction in polycystic kidney disease

Author Name : Adekoya Adebowale Olayinka

Abstract Introduction: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the commonest inherited cause of chronic kidney disease (CKD) and hypertension is an important feature in affected individuals, even those with normal kidney function. Also, endothelial dysfunction (ED) has been reported to precede hypertension in other disease conditions. However, there is paucity of data on ED hence, the need for more research. The aim of this study is to investigate activities of biomarkers of ED in PKD using immunohistochemistry (IHC) of kidney and mesenteric tissues. These biomarkers are superoxide dismutase 2 (SOD2), hemeoxygenase 1 (HO1), matrix metalloproteinase 2 (MMP2) and 8 hydroxydeoxyguanosine (8OHdG). Methods:The experimental animal were ischaemic-reperfusion models of Pkd2+/- founder mice with a null allele (ws183) for pkd2 which results from homologous recombination at exon-1 of the Pkd2 locus. Wild type mice tissues were used as controls. Activities of SOD2, HO1, MMP2 and 8OHdG were studied using IHC. Also, semi quantitative assessments of the expressions of these biomarkers was performed. Results: Heterozygous Pkd2 mice showed reduced expression of SOD2 and a greater level of HO1 staining when compared with wild type mice kidneys (p<0.0001 and p<0.05 respectively). Similarly, 8OHdG immunostaining in mesenteric vessels of wild type and heterozygous Pkd2 mice showed significant difference in the intensity (p<0.05). Lastly, MMP2 expression was predominantly extracellular but there was a statistically significant difference in staining intensity between the wild and Pkd2 KO mice (p<0.05). Conclusion: Superoxide dismutase 2, hemeoxygenase 1, matrix metalloproteinase 2 and 8 hydroxydeoxyguanosine are significant biomarkers of endothelial dysfunction and immunohistochemistry is an acceptable tool for their detection.