Lysophosphatidylcholine Offsets the Protective Effects of Bone Marrow Mesenchymal Stem Cells on Inflammatory Response and Oxidative Stress Injury of Retinal Endothelial Cells via TLR4/NF-κB Signaling.

Haijun Zhao,Yanhui He,Shengjun Wang

doi:10.1155/2021/2389029

Abstract

Diabetic retinopathy (DR), as a major cause of blindness worldwide, is one common complication of diabetes mellitus. Inflammatory response and oxidative stress injury of endothelial cells play significant roles in the pathogenesis of DR. The study is aimed at investigating the effects of lysophosphatidylcholine (LPC) on the dysfunction of high glucose- (HG-) treated human retinal microvascular endothelial cells (HRMECs) after being cocultured with bone marrow mesenchymal stem cells (BMSCs) and the underlying regulatory mechanism. Coculture of BMSCs and HRMECs was performed in transwell chambers. The activities of antioxidant-related enzymes and molecules of oxidative stress injury and the contents of inflammatory cytokines were measured by ELISA. Flow cytometry analyzed the apoptosis of treated HRMECs. HRMECs were further treated with 10-50 μg/ml LPC to investigate the effect of LPC on the dysfunction of HRMECs. Western blotting was conducted to evaluate levels of TLR4 and p-NF-κB proteins. We found that BMSCs alleviated HG-induced inflammatory response and oxidative stress injury of HRMECs. Importantly, LPC offsets the protective effects of BMSCs on inflammatory response and oxidative stress injury of HRMECs. Furthermore, LPC upregulated the protein levels of TLR4 and p-NF-κB, activating the TLR4/NF-κB signaling pathway. Overall, our study demonstrated that LPC offsets the protective effects of BMSCs on inflammatory response and oxidative stress injury of HRMECs via TLR4/NF-κB signaling.

Highlights

Diabetic retinopathy (DR), as one common complication of diabetes mellitus, is a major cause of blindness worldwide [1]
Retinal capillaries are impaired, capillary endothelial cells begin to proliferate, and the hypoxic omentum tissue releases vascular proliferation substances, which promote the formation of new blood vessels, in turn leading to proliferative diabetic retinopathy (PDR) [5, 6]
In high glucose- (HG-)treated human retinal microvascular endothelial cells (HRMECs), IL-8, IL-6, and tumor necrosis factor-α (TNF-α) contents were elevated (2-folds, ∗∗∗p < 0:001), while bone marrow mesenchymal stem cells (BMSCs) reversed (40% reduction, ∗∗p < 0:01) the increased levels of TNF-α, IL-6, and IL-8 induced by HG (Figure 2(a))

Summary

Introduction

Diabetic retinopathy (DR), as one common complication of diabetes mellitus, is a major cause of blindness worldwide [1]. Rapid increase of blood glucose in patients with diabetes results in the dysfunction of human retinal microvascular endothelial cells (HRMECs), which is embodied as inflammatory response and oxidative stress injury [3, 4]. Retinal capillaries are impaired, capillary endothelial cells begin to proliferate, and the hypoxic omentum tissue releases vascular proliferation substances, which promote the formation of new blood vessels, in turn leading to proliferative diabetic retinopathy (PDR) [5, 6]. Increased inflammation and oxidative stress are identified as key factors in the pathogenesis of DR [7]. It is urgently required to elucidate the regulation of high glucose- (HG-) induced oxidative stress and inflammation in HRMECs. The conduction of more comprehensive and logical research is required to provide more curative options for DR patients

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