title: Enhancement of lysine acetylation accelerates wound repair.
abstract: In physiopathological conditions, such as diabetes, wound healing is significantly compromised and chronic complications, including ulcers, may occur. In a mouse model of skin repair, we recently reported that wound treatment with Sirtuin activators and class I HDAC inhibitors induced keratinocyte proliferation and enhanced healing via a nitric oxide (NO) dependent mechanism. We observed an increase in total protein acetylation in the wound area, as determined by acetylation of α-tubulin and histone H3 Lysine 9. We reasoned that this process activated cell function as well as regulated gene expression to foster tissue repair. We report here that the direct activation of P300/CBP-associated factor (PCAF) by the histone acetylase activator pentadecylidenemalonate 1b (SPV-106) induced Lysine acetylation in the wound area. This intervention was sufficient to enhance repair process by a NO-independent mechanism. Hence, an impairment of PCAF and/or other GCN5 family acetylases may delay skin repair in physiopathological conditions.
authors.affiliation: Laboratorio di Biologia Vascolare e Medicina Rigenerativa; Centro Cardiologico Monzino; IRCCS; Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Spallotta
authors.forename: Chiara
authors.initials: C
authors.lastname: Cencioni
authors.forename: Stefania
authors.initials: S
authors.lastname: Straino
authors.forename: Gianluca
authors.initials: G
authors.lastname: Sbardella
authors.forename: Sabrina
authors.initials: S
authors.lastname: Castellano
authors.forename: Maurizio C
authors.initials: MC
authors.lastname: Capogrossi
authors.forename: Fabio
authors.initials: F
authors.lastname: Martelli
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaetano
keywords: Lysine acetylation; PCAF; epigenetics; keratinocyte; nitric oxide; wound healing