Open AccessInhibition of Histone Deacetylase Expands the Renal Progenitor Cell Population
Author(s) -
Eric D. de Groh,
Lisa M. Swanhart,
Chiara Cosentino,
R. Jackson,
Weixiang Dai,
Carolyn A. Kitchens,
Billy W. Day,
Thomas E. Smithgall,
Neil A. Hukriede
Publication year - 2010
Publication title -
journal of the american society of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.451
H-Index - 279
eISSN - 1533-3450
pISSN - 1046-6673
DOI - 10.1681/asn.2009080851
Subject(s) - histone deacetylase , trichostatin a , progenitor cell , biology , population , retinoic acid , microbiology and biotechnology , kidney , zebrafish , regeneration (biology) , progenitor , cancer research , stem cell , histone , biochemistry , genetics , cell culture , medicine , gene , environmental health
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.