High levels of circulating endothelial progenitor cells in patients with diabetic retinopathy are positively associated with ARHGAP22 expression

// Yu-Chuen Huang 1, 8, * , Wen-Ling Liao 2, 9, * , Jane-Ming Lin 3, 8 , Ching-Chu Chen 4, 8 , Shih-Ping Liu 5, 10, 14 , Shih-Yin Chen 1, 8 , Yu-Ning Lin 1 , Yu-Jie Lei 1 , Huan-Ting Liu 1 , Yu-Jen Chen 1, 11, 12, 13 and Fuu-Jen Tsai 1, 6, 7, 15 1 Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan 2 Center for Personalized Medicine, China Medical University Hospital, Taichung 404, Taiwan 3 Department of Ophthalmology, China Medical University Hospital, Taichung 404, Taiwan 4 Division of Endocrinology and Metabolism, China Medical University Hospital, Taichung 404, Taiwan 5 Center for Translational Medicine, China Medical University Hospital, Taichung 404, Taiwan 6 Children's Hospital of China Medical University, Taichung 404, Taiwan 7 Department of Medical Genetics, China Medical University Hospital, Taichung 404, Taiwan 8 School of Chinese Medicine, China Medical University, Taichung 404, Taiwan 9 Graduate Institute of Integrated Medicine, China Medical University, Taichung 404, Taiwan 10 Graduate Institute of Biomedical Science, China Medical University, Taichung 404, Taiwan 11 Department of Radiation Oncology, Mackay Memorial Hospital, Taipei 104, Taiwan 12 Department of Medical Research, Mackay Memorial Hospital, New Taipei City 251, Taiwan 13 Institute of Traditional Medicine, National Yang-Ming University, Taipei 112, Taiwan 14 Department of Social Work, Asia University, Taichung 413, Taiwan 15 Department of Biotechnology, Asia University, Taichung 413, Taiwan * These authors contributed equally to this work Correspondence to: Fuu-Jen Tsai, email: d0704@mail.cmuh.org.tw Yu-Jen Chen, email: chenmdphd@gmail.com Keywords: type 2 diabetes; diabetic retinopathy; circulating endothelial progenitor cells; ARHGAP22 Received: July 03, 2017      Accepted: September 21, 2017      Published: April 03, 2018 ABSTRACT Diabetic retinopathy (DR) is a common microvascular complication of diabetes. Circulating endothelial progenitor cells (EPCs) are derived from bone marrow and are characterized by pathological retinal neovascularization. Rho GTPase Activating Protein 22 ( ARHGAP22 ) is a DR susceptibility gene that interacts with its downstream regulatory protein ras-related C3 botulinum toxin substrate 1 (Rac1), to assist in endothelial cell angiogenesis and increasing capillary permeability. The aim of this study was to elucidate the relationship between ARHGAP22 expression and EPC levels in type 2 diabetes (T2D) patients with DR. Fifty T2D patients with DR were recruited. Circulating EPCs were characterized as CD31 + /vascular endothelial growth factor-2 + /CD45 dim /CD133 + and were quantified using triple staining flow cytometry. Real-time polymerase chain reaction tests were used to quantify ARHGAP22 expression. We found that T2D patients with proliferative DR had significantly lower EPC levels than those with non-proliferative DR ( P = 0.028). T2D patients with EPC levels above the median value (> 4 cells/10 5 events) had higher levels of ARHGAP22 expression ( P = 0.002). EPC levels were positively correlated with ARHGAP22 expression ( r = 0.364, P = 0.009). Among T2D patients with DR, a higher expression of ARHGAP22 was associated with higher levels of EPCs. ARHGAP22 may be involved in the mobilization or active circulation of EPCs, thus contributing to neovascularization during DR development.