Histone deacetylase inhibitor enhances recovery after AKI.

Cianciolo Cosentino C, Skrypnyk NI, Brilli LL, Chiba T, Novitskaya T, Woods C, West J, Korotchenko VN, McDermott L, Day BW, Davidson AJ, Harris RC, de Caestecker MP, Hukriede NA
J Am Soc Nephrol. 2013 24 (6): 943-53

PMID: 23620402 · PMCID: PMC3665399 · DOI:10.1681/ASN.2012111055

At present, there are no effective therapies to ameliorate injury, accelerate recovery, or prevent postinjury fibrosis after AKI. Here, we sought to identify candidate compounds that accelerate recovery after AKI by screening for small molecules that increase proliferation of renal progenitor cells in zebrafish embryos. One compound identified from this screen was the histone deacetylase inhibitor methyl-4-(phenylthio)butanoate, which we subsequently administered to zebrafish larvae and mice 24-48 hours after inducing AKI. In zebrafish, treatment with the compound increased larval survival and proliferation of renal tubular epithelial cells. In mice, treatment accelerated recovery, reduced postinjury tubular atrophy and interstitial fibrosis, and increased the regenerative capacity of actively cycling renal tubular cells by decreasing the number of cells in G2/M arrest. These data suggest that accelerating recovery may be a viable approach to treating AKI and provide proof of concept that a screen in zebrafish embryos can identify therapeutic candidates for kidney injury.

MeSH Terms (17)

Acute Kidney Injury Animals Disease Models, Animal Fibrosis Gentamicins Histone Deacetylase 1 Histone Deacetylase Inhibitors Ischemia Kidney Male Mice Mice, Inbred BALB C Phenylbutyrates Protein Synthesis Inhibitors Recovery of Function Zebrafish Zebrafish Proteins

Connections (4)

This publication is referenced by other Labnodes entities: