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Author

Kwon, H. Moo
Inflammation and Kidney Disorder Lab
Research Interests
  • TonEBP, Obesity, Cancer, Chronic inflammatory diseases, Brain disorder, Kidney disorders, Genomic instability

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TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress: organic osmolyte-dependent and -independent pathways.

Cited 1 times inthomson ciCited 12 times inthomson ci
Title
TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress: organic osmolyte-dependent and -independent pathways.
Author
Do Lee, SangChoi, Soo YounLim, Sun WooLamitina, S. ToddHo, Steffan NGo, William Y.Kwon, H. Moo
Keywords
Asporin; Heat shock protein 70; Insulin-like growth factor binding proteins; Lysophosphophatase D; Tonicity-responsive enhancer binding protein
Issue Date
201103
Publisher
AMER PHYSIOLOGICAL SOC
Citation
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v.300, no.3, pp.F707 - F715
Abstract
Lee SD, Choi SY, Lim SW, Lamitina ST, Ho SN, Go WY, Kwon HM. TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress: organic osmolyte-dependent and -independent pathways. Am J Physiol Renal Physiol 300: F707-F715, 2011. First published January 5, 2011; doi:10.1152/ajprenal.00227.2010.-TonEBP (tonicity-responsive enhancer binding protein) is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that the genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Of over 100 potentially new TonEBP-regulated genes, we selected seven for further analyses and found that their expressions were all dependent on TonEBP. RNA interference experiments showed that some of these genes, asporin, insulin-like growth factor-binding protein-5 and -7, and an extracellular lysophospholipase D, plus heat shock protein 70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation.
URI
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DOI
http://dx.doi.org/10.1152/ajprenal.00227.2010
ISSN
1931-857X
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