Chemerin/CMKLR1 Axis Promotes the Progression of Proliferative Diabetic Retinopathy.

Lihui Wang,Ying Zhang,Wencui Ding,Xinsheng Li,Chonggui Zhu,Jing Wei,Hongxia Qian,Ailing Chang,Yanan Guo,Muhittin Yurekli

doi:10.1155/2021/4468625

Abstract

Background Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes, and the levels of chemerin were associated with the severity of DR. However, there is no research on chemerin in the development of proliferative diabetic retinopathy (PDR). Therefore, our study aimed to explore the relationship between chemerin and PDR. Methods The levels of chemerin/chemokine-like receptor (CMKLR1), proinflammatory cytokines, and vascular endothelial growth factor (VEGF) in 90 cases of PDR and nonproliferative diabetic retinopathy (NPDR) patients and in high glucose (HG) stimulated human retinal pigment epithelium cells (ARPE-19) were evaluated by ELISA. Moreover, chemerin was added into HG-induced ARPE-19 cells to assess its effect on proinflammatory cytokines and VEGF. Results The levels of chemerin/CMKLR1 were higher in PDR patients than NPDR ones, and chemerin was positively correlated with CMKLR1 in PDR patients. Compared to NPDR, the secretions of proinflammatory cytokines and VEGF were increased in PDR patients and positively correlated with chemerin/CMKLR1. Additionally, chemerin activated CMKLR1 and aggravated HG-induced cell injury, inflammatory responses, and VEGF expressions in ARPE-19 cells. Conclusion Our study demonstrated that chemerin/CMKLR1 axis aggravated the progression of PDR, which suggested that inhibition of chemerin might serve as a new therapeutic approach to treat PDR.

Highlights

Diabetic retinopathy (DR) is a common diabetic microvascular complication
We first analyzed the general information of patients, and there was no significant difference (p > 0.05) on gender, age, body mass index (BMI), HbA1c, high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC) between nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) patients (Table 1)
We found that IL-1β, TNF-α, and vascular endothelial growth factor (VEGF) were positively correlated with the levels of chemerin (Figures 3(a)–3(c)) and Chemokine-International Journal of Endocrinology like receptor 1 (CMKLR1) (Figures 3(d)–3(f )), respectively, in the serum of PDR patients. us, these data suggested that either chemerin or CMKLR1 was positively correlated with the severity of inflammation in PDR patients

Summary

Introduction

Diabetic retinopathy (DR) is a common diabetic microvascular complication. Its morbidity takes up a large proportion in a variety of diabetic microvascular diseases, and it can eventually cause blindness in diabetic patients. Long-term hypoxia in the retina upregulates the expressions of related factors, leading to the overproduction of many factors, including vascular endothelial growth factor (VEGF), stimulating the division of endothelial cells, and eventually causing a mild inflammatory response as well as proliferation in the blood vessels of retina. During this process, a variety of cytokines will be produced to stimulate neovascularization. E levels of chemerin/chemokine-like receptor (CMKLR1), proinflammatory cytokines, and vascular endothelial growth factor (VEGF) in 90 cases of PDR and nonproliferative diabetic retinopathy (NPDR) patients and in high glucose (HG) stimulated human retinal pigment epithelium cells (ARPE-19) were evaluated by ELISA. Our study demonstrated that chemerin/CMKLR1 axis aggravated the progression of PDR, which suggested that inhibition of chemerin might serve as a new therapeutic approach to treat PDR

Methods

Results

Conclusion