Icariin affects cell cycle progression and proliferation of human retinal pigment epithelial cells via enhancing expression of H19

Abstract

Background Aberrant proliferation of retinal pigment epithelial (RPE) cells under pathologic condition results in the occurrence of proliferative vitreoretinopathy (PVR). Icariin (ICA)-a flavonol glucoside-has been shown to inhibit proliferation of many cell types, but the effect on RPE cells is unknown. This study aimed to clarify the inhibitory effects of ICA on RPE cells against platelet-derived growth factor (PDGF)-BB-induced cell proliferation, and discuss the regulatory function of H19 in RPE cells. Methods MTS assay was conducted to determine the effects of ICA on cell proliferation. Flow cytometry analysis was performed to detect cell cycle progression. Quantitative real-time PCR and western blot assay were used to measure the expression patterns of genes in RPE cells. Results ICA significantly suppressed PDGF-BB-stimulated RPE cell proliferation in a concentration-dependent manner. Moreover, since administration of ICA induced cell cycle G0/G1 phase arrest, the anti-proliferative activity of ICA may be due to G0/G1 phase arrest in RPE cells. At molecular levels, cell cycle regulators cyclin D1, CDK4, CDK6, p21 and p53 were modulated in response to treatment with ICA. Most importantly, H19 was positively regulated by ICA and H19 depletion could reverse the inhibitory effects of ICA on cell cycle progression and proliferation in PDGF-BB-stimulated RPE cells. Further mechanical explorations showed that H19 knockdown resulted in alternative expressions levels of cyclin D1, CDK4, CDK6, p21 and p53 under ICA treatment. Conclusions Our findings revealed that ICA was an effective inhibitor of PDGF-BB-induced RPE cell proliferation through affecting the expression levels of cell cycle-associated factors, and highlighted the potential application of ICA in PVR therapy. H19 was described as a target regulatory gene of ICA whose disruption may contribute to excessive proliferation of RPE cells, suggesting that modulation of H19 expression may be a novel therapeutic approach to treat PVR.

WITHDRAWN: Spirulina C-phycocyanin: extraction, purification, stabilization, and inhibitory potential of key enzymes rRelated to pancreas inflammation, carbohydrate digestion, and glucose metabolism

“…This is evidenced by the upregulation of key enzymes such as 5-LO, HAase, MPO, and NOX2, which are involved in the production of in ammatory eicosanoids such as prostaglandins, thromboxanes, and leukotrienes from arachidonic acid, TNFα, IL-1β, IL-6, and IL-10. Previous studies [44][45][46][47] have reported that 5-LO is responsible for the production of mediators of in ammatory reactions, and its inhibition represents a promising target for the treatment of various in ammatory pathologies. Our ndings are consistent with the work of Vilas-Boas et al [43], who reported that NADPH oxidase inhibition improves β-cell function and viability.…”