期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 24, 期 10, 页码 5695-5706出版社
WILEY
DOI: 10.1111/jcmm.15232
关键词
arctiin; diabetic retinopathy; HRCECs; Rho associated coiled-coil containing protein kinase 1; VEGF
Diabetic retinopathy (DR) is one of the most prominent microvascular complications of diabetes, which remains the leading cause of legal blindness in the world. Arctiin, a bioactive compound from Arctium lappa L., has been reported to have antidiabetic activity. In this study, we investigated the effect of arctiin on a human retinal capillary endothelial cell (HRCEC) line and how arctiin inhibits cell proliferation in high glucose (HG)-induced HRCECs. Results showed that arctiin decreased HG-induced HRCECs proliferation in a dose-dependent manner by inducing cell cycle arrest at the G0/G1 phase. Tube formation assay and immunofluorescence staining indicated that arctiin abrogated tube formation induced by HG-induced HRCECs in a dose-dependent manner via down-regulation of VEGF expression. Mechanistic study indicated that perturbation of the ROCK1/PTEN/PI3K/Akt signalling pathway plays a vital role in the arctiin-mediated anti-proliferative effect. Furthermore, pre-incubation of HRCECs with Y-27632 attenuated arctiin-induced cell cycle arrest, cell proliferation and tube formation inhibition. Y-27632 also reversed the activation of PTEN, the inactivation/dephosphorylation of PI3K/Akt and down-regulation of VEGF. Taken together, the results demonstrated that arctiin inhibits the proliferation of HG-induced HRCECs through the activation of ROCK1 and PTEN and inactivation of PI3K and Akt, resulting in down-regulation of VEGF, which inhibits endothelial cell proliferation.
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