High glucose promotes nascent nephron apoptosis via NF-κB and p53 pathways

Yun-Wen Chen, Isabelle Chenier, Shiao Ying Chang, Stella Tran, Julie R. Ingelfinger, Shao Ling Zhang

Research output: Contribution to journalArticle

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Abstract

A hyperglycemic environment in utero reduces kidney size and nephron number due to nascent nephron apoptosis. However, the underlying mechanisms are incompletely understood. The present study investigated whether the nascent nephron apoptosis promoted by high glucose is mediated via the transcription factor NF-κB and p53 signaling pathways. Neonatal mouse kidneys from the offspring of nondiabetic, diabetic, and insulin-treated diabetic dams were used for in vivo studies, and MK4 cells, an embryonic metanephric mesenchymal (MM) cell line, were used for in vitro studies. Neonatal kidneys of the offspring of diabetic mothers exhibited an increased number of apoptotic cells and reactive oxygen species (ROS) generation, enhanced NF-κB activation, and nuclear translocation of its subunits (p50 and p65 subunits) as well as phosphorylation (Ser 15) of p53 compared with kidneys of offspring of nondiabetic mothers. Insulin treatment of diabetic dams normalized these parameters in the offspring. In vitro, high-glucose (25 mM) induced ROS generation and significantly increased MK4 cell apoptosis and caspase-3 activity via activation of NF-κB pathway, with p53 phosphorylation and nuclear translocation compared with normal glucose (5 mM). These changes in a high-glucose milieu were prevented by transient transfection of small interfering RNAs for dominant negative IκBα or IKK or p53. Our data demonstrate that high glucose-induced nascent nephron apoptosis is mediated, at least in part, via ROS generation and the activation of NF-κB and p53 pathways.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume300
Issue number1
DOIs
Publication statusPublished - 2011 Jan 1

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Nephrons
Apoptosis
Glucose
Kidney
Reactive Oxygen Species
Phosphorylation
Insulin
Caspase 3
Small Interfering RNA
Transfection
Transcription Factors
Cell Count
Cell Line
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Chen, Yun-Wen ; Chenier, Isabelle ; Chang, Shiao Ying ; Tran, Stella ; Ingelfinger, Julie R. ; Zhang, Shao Ling. / High glucose promotes nascent nephron apoptosis via NF-κB and p53 pathways. In: American Journal of Physiology - Renal Physiology. 2011 ; Vol. 300, No. 1.
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High glucose promotes nascent nephron apoptosis via NF-κB and p53 pathways. / Chen, Yun-Wen; Chenier, Isabelle; Chang, Shiao Ying; Tran, Stella; Ingelfinger, Julie R.; Zhang, Shao Ling.

In: American Journal of Physiology - Renal Physiology, Vol. 300, No. 1, 01.01.2011.

Research output: Contribution to journalArticle

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