FIGURE 5.
SAHA enhances progranulin expression in haploinsufficient human cells. A, Epstein-Barr virus-immortalized human lymphoblastoid cells from a subject with a nonsense GRN R493X mutation (gray bars) and from a relative carrying wild-type alleles (black bars) were treated with SAHA for 24 h, and the relative abundance of GRN mRNA was measured by qPCR (n = 2 for 0.3 and 1 μm SAHA; n = 3 for control and 2.5 μm SAHA). *, p < 0.05 versus the GRN+/+ control; **, p < 0.05 for the indicated comparison. The dashed line indicates the relative abundance of 1. B, human dermal fibroblasts from two subjects heterozygous for GRN nonsense mutations (AA and II) and from two control subjects (HH and V) were treated as indicated, and the relative abundance of GRN mRNA was measured by qPCR. All samples were processed in parallel, and ΔΔCt values were normalized to one of the control samples (HH). The dashed line indicates the relative abundance of 1. C, cumulative data from the four cell lines shown in B plus an independent human dermal fibroblast line with a heterozygous R493X mutation is shown (n = 6 for 0 and 1 μm SAHA; n = 4 for 0.1 and 0.3 μm SAHA). *, p < 0.05 versus the vehicle control. The inset shows Western blot analysis of total cell lysates from HEK293 cells treated with the indicated concentrations of SAHA for 24 h. PGRN, progranulin.