Abstract
BackgroundPeritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD). The goal of this study was to investigate the anti-fibrotic effects of curcumin on the PF response to PD and its’ mechanism.MethodsMale Sprague–Dawley rats were infused with 20 mL of 4.25% glucose-based standard PD fluid for 8 consecutive weeks to establish PF model and then divided into five groups: Control, received sham operation and 0.9% physiological saline; PD, received 4.25% standard PD fluid; Curcumin, PD rats injected intraperitoeally with curcumin for 8 weeks at doses of 10, 20 or 40 mg/kg. Masson’s staining was performed to evaluate the extent of PF. Peritoneal Equilibration Test (PET) was conducted to assess ultrafiltration volume (UFV) and mass transfer of glucose (MTG), quantitative RT-PCR, and immunohistochemistry or western blotting were performed to measure the expression levels of inflammation and fibrosis-associated factors. We also detected the TGF-β1 in peritoneal fluid by ELISA.ResultsCompared with the control group, the PD rats showed decreased UFV (2.54 ± 0.48 to 9.87 ± 0.78 mL, p < 0.05] and increased MTG (18.99 ± 0.86 to 10.85 ± 0.65 mmol/kg, p < 0.05) as well as obvious fibroproliferative response, with markedly increased peritoneal thickness (178.33 ± 4.42 to 25.26 ± 0.32um, p < 0.05) and higher expression of a-SMA, collagen I and TGF-β1. Treatment with curcumin significantly increased UFV, reduced MTG and peritoneal thickness of PD rats. The elevated TGF-β1 in peritoneal fluid of PD rats was significantly decreased by curcumin. It attenuated the increase in protein and mRNA of TGF-β1, α-SMA and collagen I in peritoneum of PD rats. The mRNA expressions of TAK1, JNK and p38, as well as the protein expressions of p-TAK1, p-JNK and p-p38 in peritoneum of PD rats were reduced by curcumin.ConclusionsPresent results demonstrate that curcumin showed a protective effect on PD-related PF and suggest an implication of TAK1, p38 and JNK pathway in mediating the benefical effects of curcumin.
Highlights
Peritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD)
Curcumin treatment preserved peritoneal function, with significantly increased ultrafiltration volume (UFV) and reduced mass transfer of glucose (MTG) level at moderate (20 mg/kg) and high (40 mg/kg) doses compared with PD rats (P < 0.05)
Our results showed that TGF-β, α smooth muscle actin (α-SMA) and collagen I expression in mRNA and protein levels were significantly increased in the peritoneum of PD rats, and this changes were significantly attenuated by treatment with medium to large curcumin
Summary
Peritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD). High glucose can lead to inflammation and peritoneal fibrosis (PF) [2], increase the expression of transforming growth factor-β1 (TGF-β1) [3], and stimulate a complex process of peritoneal epithelialmesenchymal transition (EMT) in vivo [4]. Recent studies have found that curcumin shows antifibrotic effects on renal fibrosis through interfere with TGF-β/Smad signaling pathways, preventing inflammation initiation, inhibiting EMT, and resolving ECM excess deposition in animal models [13]. The protective effects and exact molecular mechanisms of curcumin on peritoneal fibrosis induced by peritoneal dialysis still need to be elucidated. The Smad signaling pathway is widely accepted as a canonical pathway induced by TGF-β1 in the induction of fibrosis. The balance between TGFβ1 activated Smad and BMP-activated Smad controls the peritoneal EMT and fibrosis status [15]
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