Midkine, a heparin-binding protein, is increased in the diabetic mouse kidney postmenopause

Maggie K. Diamond-Stanic, Melissa J. Romero-Aleshire, Patricia B Hoyer, Kevin Greer, James B. Hoying, Heddwen L Brooks

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Estrogen is thought to protect against the development of chronic kidney disease, and menopause increases the development and severity of diabetic kidney disease. In this study, we used streptozotocin (STZ) to induce diabetes in the 4-vinylcyclohexene diepoxide (VCD)-treated mouse model of menopause. DNA microarrays were used to identify gene expression changes in the diabetic kidney postmenopause. An ANOVA model, CARMA, was used to isolate the menopause effect between two groups of diabetic mice, diabetic menopausal (STZ/VCD) and diabetic cycling (STZ). In this diabetic study, 8,864 genes of the possible 15,600 genes on the array were included in the ANOVA; 99 genes were identified as demonstrating a >1.5-fold up- or downregulation between the STZ/VCD and STZ groups. We randomly selected genes for confirmation by real-time PCR; midkine (Mdk), immediate early response gene 3 (IEX-1), mitogen-inducible gene 6 (Mig6), and ubiquitin-specific protease 2 (USP2) were significantly increased in the kidneys of STZ/VCD compared with STZ mice. Western blot analysis confirmed that Mdk and IEX-1 protein abundance was significantly increased in the kidney cortex of STZ/VCD compared with STZ mice. In a separate study, DNA microarrays and CARMA analysis were used to identify the effect of menopause on the nondiabetic kidney; VCD-treated mice were compared with cycling mice. Of the possible 15,600 genes on the array, 9,142 genes were included in the ANOVA; 20 genes were identified as demonstrating a >1.5-fold up- or downregulation; histidine decarboxylase and vanin 1 were among the genes identified as differentially expressed in the postmenopausal nondiabetic kidney. These data expand our understanding of how hormone status correlates with the development of diabetic kidney disease and identify several target genes for further studies.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume300
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

Fingerprint

Postmenopause
Streptozocin
Kidney
Genes
Menopause
Analysis of Variance
Diabetic Nephropathies
Oligonucleotide Array Sequence Analysis
Up-Regulation
Down-Regulation
Ubiquitin-Specific Proteases
midkine
human cationic antimicrobial protein CAP 37
Histidine Decarboxylase
Kidney Cortex
Immediate-Early Genes
Microarray Analysis
Chronic Renal Insufficiency
Mitogens
4-vinyl-1-cyclohexene dioxide

Keywords

  • 4-vinylcyclohexene diepoxide
  • Estrogen
  • Microarray

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Midkine, a heparin-binding protein, is increased in the diabetic mouse kidney postmenopause. / Diamond-Stanic, Maggie K.; Romero-Aleshire, Melissa J.; Hoyer, Patricia B; Greer, Kevin; Hoying, James B.; Brooks, Heddwen L.

In: American Journal of Physiology - Renal Physiology, Vol. 300, No. 1, 01.2011.

Research output: Contribution to journalArticle

Diamond-Stanic, Maggie K. ; Romero-Aleshire, Melissa J. ; Hoyer, Patricia B ; Greer, Kevin ; Hoying, James B. ; Brooks, Heddwen L. / Midkine, a heparin-binding protein, is increased in the diabetic mouse kidney postmenopause. In: American Journal of Physiology - Renal Physiology. 2011 ; Vol. 300, No. 1.
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