Peritoneal dialysis (PD) is an important
renal replacement therapy for
end-stage renal disease (
ESRD) patients. However, its complications, such as
peritoneal fibrosis (PF) and angiogenesis can cause ultrafiltration failure and PD termination.
Histone deacetylase 6 (HDAC6) has been demonstrated to be involved in PF. However, its underlying role in peritoneal angiogenesis is still unknown and clinical value needs to be explored. In this study, we analyzed the expression of HDAC6 in the peritoneum from patients with non-PD and PD-related
peritonitis and dialysis effluent from stable PD patients. Our study revealed that HDAC6 expressed highly in the peritoneum with
peritonitis and co-stained with α-smooth muscle actin (α-SMA), a
biomarker of the myofibroblast. And the level of HDAC6 in the
dialysate increased with time and positively correlated with transforming growth factor-β1 (TGF-β1),
interleukin-6 (IL-6) and
vascular endothelial growth factor (
VEGF), and negatively with
cancer antigen 125 (CA125). In vitro, blockading HDAC6 with a selective inhibitor
tubastatin A (TA) or silencing HDAC6 with a
small interfering RNA (
siRNA) prominently decreased IL-6-stimulated
VEGF expression in cultured human peritoneal mesothelial cells (HPMCs), and inhibited proliferation and vasoformation of human umbilical vein endothelial cells (HUVECs). TA or HDAC6
siRNA also suppressed the expression of Wnt1, β-
catenin, and the phosphorylation of STAT3 in IL-6-treated HPMCs. In summary, HDAC6 inhibition protects against PD-induced angiogenesis through suppression of IL-6/STAT3 and Wnt1/β-
catenin signaling pathway, subsequently reducing the
VEGF production and angiogenesis. It could become a new therapeutic target or forecast
biomarker for PF,
inflammation, and angiogenesis in the future.