title: Human and murine kidneys show gender- and species-specific gene expression differences in response to injury.
abstract: The incidence of End Stage Renal Disease (ESRD) is approximately 50% higher in men than women. In order to understand the molecular basis of this gender disparity, we examined sex specific gene expression patterns in control and diseased, human and murine kidney samples. Using the Affymetrix platform we performed comprehensive gene expression analysis on 42 microdissected human kidney samples (glomeruli and tubules). We identified 67 genes with gender biased expression in healthy human kidneys and 24 transcripts in diseased male and female human kidneys. Similar analysis performed in mice using male and female control and doxorubicin induced nephrotic syndrome kidneys identified significantly larger number of differentially expressed transcripts. The majority of genes showing gender biased expression either in diseased human and murine kidneys were different from those differentially expressed in healthy kidneys. Only 9 sexually dimorphic transcripts were common to healthy human and murine kidneys and five showed differential regulation in both human and murine diseased kidneys. In humans, sex biased genes showed statistical enrichment only to sex chromosomes while in mice they were enriched to sex chromosomes and various autosomes. Thus we present a comprehensive analysis of gender biased genes in the kidney. We show that sexually dimorphic genes in the kidney show species specific regulation. Our results also indicate that male and female kidneys respond differently to injury. These studies could provide the basis for the development of new treatment strategies for men and women with kidney disease.
authors.affiliation: Department of Medicine/Nephrology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Han
authors.initials: H
authors.lastname: Si
authors.forename: Ramandeep S
authors.initials: RS
authors.lastname: Banga
authors.forename: Pinelopi
authors.initials: P
authors.lastname: Kapitsinou
authors.forename: Manjunath
authors.initials: M
authors.lastname: Ramaiah
authors.forename: Janis
authors.initials: J
authors.lastname: Lawrence
authors.forename: Ganesh
authors.initials: G
authors.lastname: Kambhampati
authors.forename: Antje
authors.initials: A
authors.lastname: Gruenwald
authors.forename: Erwin
authors.initials: E
authors.lastname: Bottinger
authors.forename: Daniel
authors.initials: D
authors.lastname: Glicklich
authors.forename: Vivian
authors.initials: V
authors.lastname: Tellis
authors.forename: Stuart
authors.initials: S
authors.lastname: Greenstein
authors.forename: David B
authors.initials: DB
authors.lastname: Thomas
authors.forename: James
authors.initials: J
authors.lastname: Pullman
authors.forename: Melissa
authors.initials: M
authors.lastname: Fazzari
authors.forename: Katalin
authors.initials: K
authors.lastname: Susztak
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004317:Doxorubicin / Q000633:toxicity; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D012727:Sex Characteristics; D013045:Species Specificity; D014019:Tissue Donors
chemical_list: D012333:RNA, Messenger; D004317:Doxorubicin