Wen-Jing Liang1, Hong-Wei Yang2, He-Nan Liu3, Wei Qian4, Xiao-Long Chen5. 1. Department of Ophthalmology, Shengjing Hospital, China Medical University, No.36 Sanhao Street, Heping District Shenyang, Liaoning Zip, China. Electronic address: 1611220453@qq.com. 2. Department of Ophthalmology, Shengjing Hospital, China Medical University, No.36 Sanhao Street, Heping District Shenyang, Liaoning Zip, China. Electronic address: yanghw@sj-hospital.org. 3. Department of Ophthalmology, Shengjing Hospital, China Medical University, No.36 Sanhao Street, Heping District Shenyang, Liaoning Zip, China. Electronic address: liuhn@sj-hospital.org. 4. Medical Imaging Informatics Laboratory College of Engineering, University of Texas, El Paso 500 West University Avenue El Paso, TX 79968, United States of America. Electronic address: wqian@utep.edu. 5. Department of Ophthalmology, Shengjing Hospital, China Medical University, No.36 Sanhao Street, Heping District Shenyang, Liaoning Zip, China. Electronic address: chenxiaolongsj@163.com.
Abstract
AIMS: Diabetic retinopathy (DR) is the main cause of blindness in adults and investigating new therapeutic targets for DR is necessary. This study aimed to investigate the effect of high-mobility group box 1 (HMGB1) protein and its mechanism in diabetic retinopathy (DR) were investigated. MAIN METHODS: Human retinal endothelial cells (HREC) were uesd for chip-seq. Sprague Dawley (SD) rats were randomly divided into control group, HMGB1 group, diabetes mellitus (DM) combined with HMGB1 siRNA group, and DM group. Next, eyeballs were removed and retinas were detached for western blot. The DM model of cell was built by increasing the glucose concentration in cell culture medium. The regulation of HMGB1 was achieved by short hairpin (sh)-HMGB1 transfection, then, the transfected cells were harvested for luciferase assay, western blot and qRT-PCR analyses as well as proliferation and apoptosis detection. KEY FINDINGS: Chip-seq and luciferase assay showed the possible transcription factor functions of HMGB1 and IKB-α was one of the HMGB1 binding sites. In vivo and in vitro results indicated high expression of HMGB1 and NF-kB and low expression of IKB-α in DR and the expression of IKB-α and NF-kB was regulated by HMGB1. Moreover, cell assays showed that HMGB1 inhibited cell proliferation and promoted apoptosis. SIGNIFICANCE: The results from the present study showed that HMGB1 may be involved in the pathogenesis of DR as a transcription factor through NF-kB pathway. Therefore, blockade of HMGB1 may be a new method for the treatment of DR.
AIMS: Diabetic retinopathy (DR) is the main cause of blindness in adults and investigating new therapeutic targets for DR is necessary. This study aimed to investigate the effect of high-mobility group box 1 (HMGB1) protein and its mechanism in diabetic retinopathy (DR) were investigated. MAIN METHODS:Human retinal endothelial cells (HREC) were uesd for chip-seq. Sprague Dawley (SD) rats were randomly divided into control group, HMGB1 group, diabetes mellitus (DM) combined with HMGB1 siRNA group, and DM group. Next, eyeballs were removed and retinas were detached for western blot. The DM model of cell was built by increasing the glucose concentration in cell culture medium. The regulation of HMGB1 was achieved by short hairpin (sh)-HMGB1 transfection, then, the transfected cells were harvested for luciferase assay, western blot and qRT-PCR analyses as well as proliferation and apoptosis detection. KEY FINDINGS: Chip-seq and luciferase assay showed the possible transcription factor functions of HMGB1 and IKB-α was one of the HMGB1 binding sites. In vivo and in vitro results indicated high expression of HMGB1 and NF-kB and low expression of IKB-α in DR and the expression of IKB-α and NF-kB was regulated by HMGB1. Moreover, cell assays showed that HMGB1 inhibited cell proliferation and promoted apoptosis. SIGNIFICANCE: The results from the present study showed that HMGB1 may be involved in the pathogenesis of DR as a transcription factor through NF-kB pathway. Therefore, blockade of HMGB1 may be a new method for the treatment of DR.