Curcumin suppresses epithelial-to-mesenchymal transition of peritoneal mesothelial cells (HMrSV5) through regulation of transforming growth factor-activated kinase 1 (TAK1)

Abstract

Objective Peritoneal fibrosis remains a serious complication of long-term peritoneal dialysis (PD) leading to peritoneal membrane ultrafiltration failure. Epithelial–mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is a key process of peritoneal fibrosis. Curcumin has been previously shown to inhibit EMT of renal tubular epithelial cells and prevent renal fibrosis. There are only limited reports on inhibition of PMCs-EMT by curcumin. This study aimed to investigate the effect of curcumin on the regulation of EMT and related pathway in PMCs treated with glucose-based PD. Methods EMT of human peritoneal mesothelial cells (HMrSV5) was induced with glucose-based peritoneal dialysis solutions (PDS). Cells were divided into a control group, PDS group, and PDS group receiving varied concentrations of curcumin. Cell Counting Kit-8 (CCK-8) assay was used to measure cell viability, and a transwell migration assay was used to verify the capacity of curcumin to inhibit EMT in HMrSV5 cells. Real-time quantitative PCR and western blot were used to detect the expression of genes and proteins associated with the EMT. Results High glucose PDS decreased cell viability and increased migratory capacity. Curcumin reversed growth inhibition and migration capability of human peritoneal mesothelial cells (HPMCs). In HMrSV5 cells, high glucose PDS also decreased expression of epithelial markers, and increased expression of mesenchymal markers, a characteristic of EMT. Real-time RT-PCR and western blot revealed that, compared to the 4.25% Dianeal treated cells, curcumin treatment resulted in increased expression of E-cadherin (epithelial marker), and decreased expression of α-SMA (mesenchymal markers) ( P < 0.05). Furthermore, curcumin reduced mRNA expression of two extracellular matrix protein, collagen I and fibronectin. Curcumin also reduced TGF-β1 mRNA and supernatant TGF-β1 protein content in the PDS-treated HMrSV5 cells ( P < 0.05). Furthermore, it significantly reduced protein expression of p-TAK1, p-JNK and p-p38 in PDS-treated HMrSV5 cells. Conclusions Our results demonstrate that curcumin showed an obvious protective effect on PDS-induced EMT of HMrSV5 cells and suggest implication of the TAK1, p38 and JNK pathway in mediating the effects of curcumin in EMT of MCs.

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Nanomaterials as Inhibitors of Epithelial Mesenchymal Transition in Cancer Treatment

“…Curcumin, a phytochemical derived from Curcuma longa, has been largely exploited in combination with traditional chemotherapeutics to increase their anticancer efficacy [133]. Besides, recent reports showed that curcumin suppresses EMT and metastasis in various tumor cells [134][135][136].…”

New Paradigms to Assess Consequences of Long-Term, Low-Dose Curcumin Exposure in Lung Cancer Cells

“…These findings were corroborated by the oncology array platform, which demonstrated that long-term, low-dose curcumin favours upregulation of anti-carcinogenic, and downregulation of pro-carcinogenic proteins, many of which are associated with epithelial to mesenchymal transition (EMT). Curcumin has previously been shown to play a role in preventing or reversing the generation of an EMT phenotype [16][17][18][19], albeit at single, non-pharmacologic high doses ranging from 10 to 80 µM. Such high doses are unlikely to be attained clinically, making it difficult to interpret and translate mechanistic relevance to prevention strategies that are typified by sub-micromolar systemic curcuminoid availability.…”