Valproic Acid, a Histone Deacetylase Inhibitor, Decreases Proliferation ofand Induces Specific Neurogenic Differentiation of Canine Adipose Tissue-Derived StemCells

[摘要] References(39)Cited-By(2)Adipose tissue-derived stem cells (ADSCs) isolated from adult tissue havepluripotent differentiation and self-renewal capability. The tissue source of ADSCs can beobtained in large quantities and with low risks, thus highlighting the advantages of ADSCsin clinical applications. Valproic acid (VPA) is a widely used antiepileptic drug, whichhas recently been reported to affect ADSC differentiation in mice and rats; however, fewstudies have been performed on dogs. We aimed to examine the in vitroeffect of VPA on canine ADSCs. Three days of pretreatment with VPA decreased theproliferation of ADSCs in a dose-dependent manner; VPA concentrations of 4 mM and aboveinhibited the proliferation of ADSCs. In parallel, VPA increased p16 andp21 mRNA expression, suggesting that VPA attenuated the proliferativeactivity of ADSCs by activating p16 and p21. Furthermore, the effects of VPA onadipogenic, osteogenic or neurogenic differentiation were investigated morphologically.VPA pretreatment markedly promoted neurogenic differentiation, but suppressed theaccumulation of lipid droplets and calcium depositions. These modifications of ADSCs byVPA were associated with a particular gene expression profile, viz., an increase inneuronal markers, that is, NSE, TUBB3 andMAP2, a decrease in the adipogenic marker, LPL, but nochanges in osteogenic markers, as estimated by reverse transcription-PCR analysis. Theseresults suggested that VPA is a specific inducer of neurogenic differentiation of canineADSCs and is a useful tool for studying the interaction between chromatin structure andcell fate determination.

[学科分类] 兽医学

[关键词] adipose tissue-derived stem cell;cell proliferation;histone deacetylase inhibitor;pluripotency;valproic acid