title: Inhibition of histone deacetylase expands the renal progenitor cell population.
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.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: de Groh
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Swanhart
authors.forename: Chiara Cianciolo
authors.initials: CC
authors.lastname: Cosentino
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Jackson
authors.forename: Weixiang
authors.initials: W
authors.lastname: Dai
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Kitchens
authors.forename: Billy W
authors.initials: BW
authors.lastname: Day
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Smithgall
authors.forename: Neil A
authors.initials: NA
authors.lastname: Hukriede
mesh_terms: 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
chemical_list: C549619:4-(phenylthio)butanoic acid; D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D013440:Sulfides; D014212:Tretinoin