Bo Wu1, James D Brooks. 1. Department of Urology, Stanford University School of Medicine, Stanford, California 94305-5118, USA.
Abstract
PURPOSE: Loss of renal function is often the impetus for operative intervention in renal obstruction cases. Obstructive nephropathy is characterized by discrete morphological and physiological changes, including tubular dilatation, apoptosis and atrophy as well as interstitial cellular infiltration and progressive interstitial fibrosis. We hypothesized that gene expression alterations correlate with obstructive nephropathy and could serve as biomarkers for early intervention. MATERIALS AND METHODS: C57BL/6 mice were subjected to unilateral ureteral obstruction or sham surgery at postnatal day 21. Kidneys were harvested 1, 2, 5 and 9 days postoperatively. RNA was extracted from kidneys and comprehensive gene expression profiling was performed with microarrays. IPA® pathway analysis software was used to analyze the biological function and gene networks of gene expression data. RESULTS: Microarray analysis revealed more than 1,800 transcripts that were up-regulated or down-regulated during days 1 through 9 after obstruction, including many previously reported transcripts (FOS, CD44, CLU, SPP1 and EGF). Pathway analysis showed significant enrichment of transcripts in cell activation/differentiation, immune/inflammatory responses, cell cycle, metabolic process and transport. Network analysis using IPA showed that transcriptional regulatory pathways involving CEBPB and HNF4A are involved in obstructive nephropathy. CONCLUSIONS: This data set provides a foundation for development of biomarkers for obstructive nephropathy.
PURPOSE: Loss of renal function is often the impetus for operative intervention in renal obstruction cases. Obstructive nephropathy is characterized by discrete morphological and physiological changes, including tubular dilatation, apoptosis and atrophy as well as interstitial cellular infiltration and progressive interstitial fibrosis. We hypothesized that gene expression alterations correlate with obstructive nephropathy and could serve as biomarkers for early intervention. MATERIALS AND METHODS: C57BL/6 mice were subjected to unilateral ureteral obstruction or sham surgery at postnatal day 21. Kidneys were harvested 1, 2, 5 and 9 days postoperatively. RNA was extracted from kidneys and comprehensive gene expression profiling was performed with microarrays. IPA® pathway analysis software was used to analyze the biological function and gene networks of gene expression data. RESULTS: Microarray analysis revealed more than 1,800 transcripts that were up-regulated or down-regulated during days 1 through 9 after obstruction, including many previously reported transcripts (FOS, CD44, CLU, SPP1 and EGF). Pathway analysis showed significant enrichment of transcripts in cell activation/differentiation, immune/inflammatory responses, cell cycle, metabolic process and transport. Network analysis using IPA showed that transcriptional regulatory pathways involving CEBPB and HNF4A are involved in obstructive nephropathy. CONCLUSIONS: This data set provides a foundation for development of biomarkers for obstructive nephropathy.
Authors: Shibdas Banerjee; Anny Chuu-Yun Wong; Xin Yan; Bo Wu; Hongjuan Zhao; Robert J Tibshirani; Richard N Zare; James D Brooks Journal: Sci Rep Date: 2019-07-29 Impact factor: 4.379