Preferential expression of insulin-like growth factor binding proteins- 1, -3, and -5 during early diabetic renal hypertrophy in rats

I. S. Park, H. Kiyomoto, F. Alvarez, Y. C. Xu, H. E. Abboud, S. L. Abboud

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The renal insulin-like growth factor-I (IGF-I) system has been implicated in the pathogenesis of renal hypertrophy, altered hemodynamics, and extracellular matrix expansion associated with early diabetes. The relative abundance of IGF binding proteins (IGFBPs) in the renal microenvironment may modulate IGF-I actions. However, the precise IGFBPs expressed in the glomerular and tubulointerstitial compartments during diabetic renal growth have not been characterized. In the present study, in situ hybridization studies were performed to examine the expression of IGFBP- 1 to -6 messenger RNAs (mRNAs) 3, 7, and 14 days after streptozotocin (STZ) injection in rats. In control, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed with a predominance of IGFBP-5. The onset of renal hypertrophy in STZ-induced diabetes was associated with a rapid and site- specific induction of IGFBP-1, -3, and -5 mRNAs. In contrast, basal expression of IGFBP-2, -4, and -6 mRNAs was not altered in diabetic rats. IGFBP-5 mRNA expression increased in diabetic glomeruli, cortical, and inner medullary peritubular interstitial cells at days 3, 7, and 14. Although normal glomeruli failed to express IGFBP-3, it was induced concomitantly with IGFBP-5 in diabetic glomeruli and cortical peritubular interstitial cells. IGFBP-1 mRNA levels also increased in cortical tubular cells at each time point tested. Peak induction of IGFBP-3 and -5 was observed at day 3, whereas IGFBP-1 was delayed until day 7. IGFBP-1, -3, and -5 mRNA levels declined by day 14, but remained persistently elevated above control. By immunoperoxidase staining, similar alterations in the pattern of IGFBP-3 and -5 protein expression were observed at each time point. The preferential and site- specific increase in IGFBP-1, -3, and -5 suggest that these IGFBPs may regulate the local autocrine and/or paracrine actions of IGF-I and contribute to the pathogenesis of the early manifestations of diabetic nephropathy.

Original languageEnglish (US)
Pages (from-to)1000-1010
Number of pages11
JournalAmerican Journal of Kidney Diseases
Volume32
Issue number6
StatePublished - 1998

Fingerprint

Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor Binding Protein 3
Hypertrophy
Kidney
Messenger RNA
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Protein 4
Insulin-Like Growth Factor Binding Protein 2
Experimental Diabetes Mellitus
Diabetic Nephropathies
Streptozocin
In Situ Hybridization
Extracellular Matrix
Hemodynamics
Staining and Labeling
Injections
Growth

Keywords

  • Diabetes
  • Gene expression
  • Insulin-like growth factor binding proteins
  • Kidney

ASJC Scopus subject areas

  • Nephrology

Cite this

Park, I. S., Kiyomoto, H., Alvarez, F., Xu, Y. C., Abboud, H. E., & Abboud, S. L. (1998). Preferential expression of insulin-like growth factor binding proteins- 1, -3, and -5 during early diabetic renal hypertrophy in rats. American Journal of Kidney Diseases, 32(6), 1000-1010.

Preferential expression of insulin-like growth factor binding proteins- 1, -3, and -5 during early diabetic renal hypertrophy in rats. / Park, I. S.; Kiyomoto, H.; Alvarez, F.; Xu, Y. C.; Abboud, H. E.; Abboud, S. L.

In: American Journal of Kidney Diseases, Vol. 32, No. 6, 1998, p. 1000-1010.

Research output: Contribution to journalArticle

Park, I. S. ; Kiyomoto, H. ; Alvarez, F. ; Xu, Y. C. ; Abboud, H. E. ; Abboud, S. L. / Preferential expression of insulin-like growth factor binding proteins- 1, -3, and -5 during early diabetic renal hypertrophy in rats. In: American Journal of Kidney Diseases. 1998 ; Vol. 32, No. 6. pp. 1000-1010.
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