PUBLICATION
Inhibition of Histone Deacetylase Expands the Renal Progenitor Cell Population
- Authors
- de Groh, E.D., Swanhart, L.M., Cosentino, C.C., Jackson, R.L., Dai, W., Kitchens, C.A., Day, B.W., Smithgall, T.E., and Hukriede, N.A.
- ID
- ZDB-PUB-100420-8
- Date
- 2010
- Source
- Journal of the American Society of Nephrology : JASN 21(5): 794-802 (Journal)
- Registered Authors
- Hukriede, Neil, Jackson, Rachel
- Keywords
- none
- MeSH Terms
-
- Animals
- Butyrates/pharmacology*
- Cell Proliferation
- Drug Evaluation, Preclinical
- Embryonic Stem Cells/drug effects*
- Histone Deacetylase Inhibitors/pharmacology*
- Kidney/drug effects*
- Kidney/embryology
- Regeneration/drug effects*
- Signal Transduction/drug effects
- Structure-Activity Relationship
- Sulfides/pharmacology*
- Tretinoin/metabolism
- Zebrafish
- PubMed
- 20378823 Full text @ J. Am. Soc. Nephrol.
Citation
de Groh, E.D., Swanhart, L.M., Cosentino, C.C., Jackson, R.L., Dai, W., Kitchens, C.A., Day, B.W., Smithgall, T.E., and Hukriede, N.A. (2010) Inhibition of Histone Deacetylase Expands the Renal Progenitor Cell Population. Journal of the American Society of Nephrology : JASN. 21(5):794-802.
Abstract
One of the first hallmarks of kidney regeneration is the reactivation of genes normally required during organogenesis. Identification of chemicals with the potential to enhance this reactivation could therapeutically promote kidney regeneration. Here, we found that 4-(phenylthio)butanoic acid (PTBA) expanded the expression domains of molecular markers of kidney organogenesis in zebrafish. PTBA exhibits structural and functional similarity to the histone deacetylase (HDAC) inhibitors 4-phenylbutanoic acid and trichostatin A; treatment with these HDAC inhibitors also expanded the renal progenitor cell population. Analyses in vitro and in vivo confirmed that PTBA functions as an inhibitor of HDAC activity. Furthermore, PTBA-mediated renal progenitor cell expansion required retinoic acid signaling. In summary, these results support a mechanistic link among renal progenitor cells, HDAC, and the retinoid pathway. Whether PTBA holds promise as a therapeutic agent to promote renal regeneration requires further study.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping