Tasquinimod efficacy and S100A9 expression in glucose-treated HREC cells

Abstract

Purpose Diabetic retinopathy (DR) is one of the leading causes of blindness in working-aged people. Few studies were on the relationship between S100 Calcium Binding Protein A9 (S100A9) protein and DR, and none on endothelial cells induced by tasquinimod in high glucose. Therefore, we assessed the relationship between tasquinimod and S100A9 in DR. Methods DR pathogenesis was simulated using high-glucose-induced human retinal endothelial cells (HRECs) to study the mRNA expression of s100a9, thrombospondin-1 (tsp-1), hypoxia-inducible factor 1-alpha (hif1-a), intercellular adhesion molecule 1 (icam-1), and vascular endothelial growth factor (vegf) after tasquinimod treatment. The protein expression of S100A9, TSP-1, extracellular signal-regulated kinase (ERK), ICAM-1 and VEGF was also analyzed. Result A total of 28 eyes of 26 patients were included in this experiment. A significantly higher expression of S100A9 as well as enhanced proliferation and mobility was observed in the high-glucosetreated HRECs compared with that in low-glucosetreated cells. However, these were significantly inhibited when treated with high glucose with 50 lM tasquinimod. The mRNA expression of tsp-1 was increased, whereas that of hif1-a, icam-1 and vegf was decreased after tasquinimod treatment. Western blot indicated the increased TSP-1 but decreased ERK, ICAM-1 and VEGF expression after treating with tasquinimod. Conclusion High glucose promoted the expression of s100a9, S100A9 protein in DR patients and HRECs. Tasquinimod inhibited the proliferation, migration and lumen formation of HRECs under a high glucose environment. Tasquinimod might play a vital role in inhibiting angiogenesis through inducing TSP-1 and inhibiting VEGF, ICAM-1 and ERK.

Dimethyl Fumarate Triggers the Antioxidant Defense System in Human Retinal Endothelial Cells through Nrf2 Activation

“…Interestingly, in the literature, there is a high variability in both experimental settings and results regarding the status of HREC/endothelial cells under high glucose concentrations (≥25 mM). In agreement with our data, other in vitro studies showed no relevant changes at 24 h [ 34 , 35 ]; however, at the same time of exposure, Jin et al [ 36 ] recently reported that 30 mM glucose in HREC induces proliferation (about +20%). These discrepancies in both the acute and chronic hyper-glucose-induced effects may be related to different experimental settings among laboratories, including the source and passage of HREC and the method used to assess cell survival, with the majority of in vitro studies performing the MTT assay.…”

“…In vitro studies report that endothelial cells are susceptible to high-glucose concentrations, although with notable differences among laboratories [ 34 , 35 , 36 , 37 , 38 ]. Before evaluating potential cytoprotective effects of DMF treatment in HREC cells under high glucose conditions, we first performed experiments to select the best time of exposure and concentrations of glucose leading to a significant cell viability impairment in HREC.…”

Identification of a shared gene signature and biological mechanism between diabetic foot ulcers and cutaneous lupus erythemnatosus by transcriptomic analysis

“…The pharmacological activity of taquinmod is more associated with anti-vascular and anti-prostate cancer effects (Isaacs et al, 2006;Olsson et al, 2010;Boros and Vécsei, 2020). In the pathological environment of high glucose, taquinmod inhibits proliferation, migration and lumen formation of human retinal endothelial cells (Jin et al, 2022). Ribavirin, as an antiviral drug, is considered as a potential candidate for the treatment of HFMD (Leung et al, 2022).…”