HDGF derived from Müller cells enhances the activation of microglia in diabetic retinopathy
Aowang Qiu1
Wenjie Yin1
Ningyu Wang1
Xin Wang2
Qinghuai Liu1
Weiwei Zhang1
1.Department of Ophthalmology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210029,China2.Department of Endocrinology,Jiangsu Province Hospital of TCM/the Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing,Jiangsu 210029,China
摘要：Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear.We measured HDGF levels in the aqueous humor and found that HDGF was increased in DR but decreased after anti-angiogenesis treatment.Using public single-cell RNA sequencing datasets,we found that elevated HDGF in DR was mainly produced by Müller cells and targeted microglia.Additionally,integrin beta 2(Itgb2),a target gene of HDGF that induces microglial activation,was significantly upregulated in DR.To verify these results,we performed enzyme-linked immunosorbent assays,quantitative reverse transcription-PCR,Western blotting,and fluorescence immunostaining in cultured Müller and microglial cells treated with HDGF or anti-HDGF,as well as in DR mice receiving intravitreal injections of HDGF or its antibody.Exogenous HDGF further promoted microglial activation,migration,and secretion of pro-inflammatory cytokines,while neutralization of HDGF suppressed these effects caused by high glucose.Furthermore,the HDGF receptor nucleolin was overexpressed in microglia under high glucose stimulation.Therefore,blocking HDGF from Müller cells in DR reduced the excessive inflammatory response in microglia,highlighting HDGF as a potential therapeutic target.
机标关键词：hdgfcellsfromactivationderiveddiabeticenhancesller
分类号：R774.1(视网膜及视神经疾病)
论文发表日期：2026-01-30
在线出版日期：2026-01-29（本平台首次上网日期，不代表文献的发表时间）
页数：13( 63-75 )
英文信息