D-glucose-induced dysmorphogenesis of embryonic kidney

Yashpal S. Kanwar, Zheng Z. Liu, Anil Kumar, M. Irtaza Usman, Jun Wada, Elisabeth I. Wallner

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

An organ culture system was used to study the effect of D-glucose on embryonic kidneys, and to delineate the mechanism(s) relevant to their dysmorphogenesis. Metanephroi were cultured in the presence of 30 mM D- glucose. A notable reduction in the size and population of nephrons was observed. Ureteric bud branches were rudimentary and the acuteness of their tips, the site of nascent nephron formation, was lost. Metanephric mesenchyme was atrophic, had reduced cell replication, and contained numerous apoptotic cells. Competitive reverse transcriptase-PCR analyses and immunoprecipitation studies indicated a decrease in expression of heparan sulfate proteoglycan (perlecan). Status of activated protein-2 was evaluated since its binding motifs are present in the promoter region of the perlecan gene. Decreased binding activity of activated protein-2, related to its phosphorylation, was observed. D-glucose-treated explants also had reduced levels of cellular ATP. Exogenous administration of ATP restored the altered metanephric morphology and reduced [35S]sulfate-incorporated radioactivity associated with perlecan. The data suggest that D-glucose adversely affects the metanephrogenesis by perturbing various cellular phosphorylation events involved in the transcriptional and translational regulation of perlecan. Since perlecan modulates epithelial/mesenchymal interactions, its deficiency may have led to the metanephric dysmorphogenesis and consequential atrophy of the mesenchyme exhibiting accelerated apoptosis.

Original languageEnglish
Pages (from-to)2478-2488
Number of pages11
JournalJournal of Clinical Investigation
Volume98
Issue number11
Publication statusPublished - Dec 1 1996
Externally publishedYes

Fingerprint

Kidney
Glucose
Nephrons
Mesoderm
Adenosine Triphosphate
Phosphorylation
Heparan Sulfate Proteoglycans
Organ Culture Techniques
Population Density
Reverse Transcriptase Polymerase Chain Reaction
Immunoprecipitation
Genetic Promoter Regions
Radioactivity
Sulfates
Atrophy
Proteins
perlecan
Apoptosis
Genes

Keywords

  • adenosine triphosphate
  • apoptosis
  • diabetes
  • kidney development
  • proteoglycans

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kanwar, Y. S., Liu, Z. Z., Kumar, A., Usman, M. I., Wada, J., & Wallner, E. I. (1996). D-glucose-induced dysmorphogenesis of embryonic kidney. Journal of Clinical Investigation, 98(11), 2478-2488.

D-glucose-induced dysmorphogenesis of embryonic kidney. / Kanwar, Yashpal S.; Liu, Zheng Z.; Kumar, Anil; Usman, M. Irtaza; Wada, Jun; Wallner, Elisabeth I.

In: Journal of Clinical Investigation, Vol. 98, No. 11, 01.12.1996, p. 2478-2488.

Research output: Contribution to journalArticle

Kanwar, YS, Liu, ZZ, Kumar, A, Usman, MI, Wada, J & Wallner, EI 1996, 'D-glucose-induced dysmorphogenesis of embryonic kidney', Journal of Clinical Investigation, vol. 98, no. 11, pp. 2478-2488.
Kanwar YS, Liu ZZ, Kumar A, Usman MI, Wada J, Wallner EI. D-glucose-induced dysmorphogenesis of embryonic kidney. Journal of Clinical Investigation. 1996 Dec 1;98(11):2478-2488.
Kanwar, Yashpal S. ; Liu, Zheng Z. ; Kumar, Anil ; Usman, M. Irtaza ; Wada, Jun ; Wallner, Elisabeth I. / D-glucose-induced dysmorphogenesis of embryonic kidney. In: Journal of Clinical Investigation. 1996 ; Vol. 98, No. 11. pp. 2478-2488.
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