Prepubertal onset of diabetes prevents expression of renal cortical connective tissue growth factor

William J. Langer, Kay Devish, Pamela K. Carmines, Pascale H. Lane

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Puberty unmasks or accelerates the nephropathy of diabetes mellitus (DM). We performed focused microarray analysis to test the hypothesis that one or more genes in the transforming growth factor beta (TGF-β) signaling system would be differentially regulated in male rats depending on their age at onset of DM. Littermates were started on the 6-week protocol at 4 weeks or 14 weeks of age. Renal cortical RNA was isolated and analyzed using gene chips with more than 30,000 transcripts. Age-specific effects of DM were demonstrated for 1,760 transcripts. Analysis then focused on 89 genes involved in the TGF-β signaling pathway. Three of these genes showed age-dependent responses to DM, confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Connective tissue growth factor (CTGF) mRNA and protein were both increased ∼30% in the renal cortex 6 weeks after adult-onset DM, with no alteration in either parameter after juvenile onset. Follistatin and avian myelocytomatosis viral oncogene homolog mRNA both showed a similar age-related pattern of response to DM, but protein levels did not parallel mRNA for either of these gene products. Given the known roles of CTGF in progressive nephropathies, it is an attractive candidate to explain pubertal acceleration or unmasking of the kidney disease of diabetes.

Original languageEnglish (US)
Pages (from-to)275-283
Number of pages9
JournalPediatric Nephrology
Volume23
Issue number2
DOIs
StatePublished - Feb 2008

Keywords

  • Follistatin
  • Microarray studies
  • Myc
  • Puberty
  • Transforming growth factor β

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

Fingerprint Dive into the research topics of 'Prepubertal onset of diabetes prevents expression of renal cortical connective tissue growth factor'. Together they form a unique fingerprint.

  • Cite this