Inhibition of histone deacetylase expands the renal progenitor cell population.
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.
de Groh
Eric D
ED
Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Swanhart
Lisa M
LM
Cosentino
Chiara Cianciolo
CC
Jackson
Rachel L
RL
Dai
Weixiang
W
Kitchens
Carolyn A
CA
Day
Billy W
BW
Smithgall
Thomas E
TE
Hukriede
Neil A
NA
D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D049109:Cell Proliferation; D004353:Drug Evaluation, Preclinical; D053595:Embryonic Stem Cells / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000196:embryology; D012038:Regeneration / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000494:pharmacology*; D014212:Tretinoin / Q000378:metabolism; D015027:Zebrafish
C549619:4-(phenylthio)butanoic acid; D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D013440:Sulfides; D014212:Tretinoin