Abstract P166: Identification of Cyr61 and Tfgbi as Hypertensive Renal LEC Genes

Abstract

Increased renal lymphatic density is observed in various experimental models of hypertension. To identify differentially expressed genes in lymphatic endothelial cells (LECs) from hypertensive kidneys, we utilized Gene Expression Omnibus (GEO) which was developed by the NIH NCBI. GEO is an international public repository that archives and distributes high-throughput functional genomic data sets such as microarray and next-generation sequencing data. GEO2R is an interactive web tool that allows users to compare samples across experimental conditions in a GEO Series in order to identify genes that are differentially expressed. Results are presented as a table of genes ordered by significance. Using GEO2R, the search terms “lymphatic” and “hypertensive kidney” were used to identify studies of LEC-associated genes and renal hypertension-associated genes. Among the search results for LEC genes, 4 studies were chosen that were done in mice comparing: a) murine primary LECs vs. murine endothelial SVEC4-10 cell line, b) collecting lymphatic endothelium of mice with 293EBNA xenografts with and without overexpression of VEGFD, c) LECs from afferent and efferent lymphatic vessels, and d) LECs and blood vascular endothelial cells from mouse intestine. For renal hypertensive genes, we chose a study that reported differentially expressed genes in kidneys of mice treated with angiotensin II for 1, 3 or 7 days compared to controls. From all of these lists, the top 250 differentially expressed genes were chosen. The list of renal genes was crossed with a combined list of LEC genes to obtain potential “LEC genes differentially expressed in hypertensive kidneys”. This yielded a list of 40 genes for which mRNA expression was tested in the kidneys of mice from 3 different models of hypertension: nitric oxide inhibition-induced, salt-sensitive, and angiotensin II-induced. Among the differentially expressed genes, Cyr61 and Tgfbi were elevated significantly in all 3 hypertensive models. Cyr61 is a well-known inducer of angiogenesis. Tfgbi is involved in LEC adhesion to extracellular matrix under hypoxic conditions. The upregulation of these two genes likely play a major role in renal LEC function during hypertension.