Secreted Protein Acidic and Rich in Cysteine Mediates the Development and Progression of Diabetic Retinopathy

被引:7
作者
Luo, Liying [1 ]
Sun, Xi [2 ]
Tang, Min [3 ,4 ]
Wu, Jiahui [3 ,4 ]
Qian, Tianwei [3 ,4 ]
Chen, Shimei [3 ,4 ]
Guan, Zhiyuan [5 ]
Jiang, Yanyun [1 ]
Fu, Yang [3 ,4 ]
Zheng, Zhi [3 ,4 ]
机构
[1] Shanghai Jiao Tong Univ, Tongren Hosp, Dept Ophthalmol, Sch Med, Shanghai, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Hematol, Sch Med, Shanghai, Peoples R China
[3] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Ophthalmol, Sch Med, Shanghai, Peoples R China
[4] Shanghai Engn Ctr Visual Sci & Photomed, Shanghai Key Lab Ocular Fundus Dis, Shanghai, Peoples R China
[5] Tongji Univ, Dept Orthoped, Shanghai Peoples Hosp 9, Shanghai, Peoples R China
关键词
SPARC; diabetic retinopathy; integrin b1; angiogenesis; HRCECs; ENDOTHELIAL GROWTH-FACTOR; SPARC; VEGF; EXPRESSION; APOPTOSIS; FIBRONECTIN; MATRIX;
D O I
10.3389/fendo.2022.869519
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Backgrounds: Diabetic retinopathy (DR) is one of the most severe microvascular complications of diabetes mellitus (DM). Secreted protein acidic and rich in cysteine (SPARC) has been found to play an important role in many diseases, but its role and mechanism in DR remain unknown. Methods: We studied the role of SPARC and integrin beta 1 in vascular pathophysiology and identified potential therapeutic translation. The SPARC levels were tested in human serum and vitreous by ELISA assay, and then the Gene Expression Omnibus (GEO) dataset was used to understand the key role of the target gene in DR. In human retinal capillary endothelial cells (HRCECs), we analyzed the mRNA and protein level by RT-PCR, immunohistochemistry, and Western blotting. The cell apoptosis, cell viability, and angiogenesis were analyzed by flow cytometry, CCK-8, and tube formation. Results: In this study, we investigated the role of SPARC in the development and progression of human DR and high glucose-induced HRCEC cells and found that the SPARC-ITGB1 signaling pathway mimics early molecular and advanced neurovascular pathophysiology complications of DR. The result revealed that DR patients have a high-level SPARC expression in serum and vitreous. Knockdown of SPARC could decrease the expressions of inflammatory factors and VEGFR, inhibit cell apoptosis and angiogenesis, and increase cell viability by regulating integrin beta 1 in HRCECs. Conclusion: SPARC promotes diabetic retinopathy via the regulation of integrin beta 1. The results of this study can provide a potential therapeutic application for the treatment of DR.
引用
收藏
页数:14
相关论文
共 46 条
[1]   VASCULAR ENDOTHELIAL GROWTH-FACTOR IN OCULAR FLUID OF PATIENTS WITH DIABETIC-RETINOPATHY AND OTHER RETINAL DISORDERS [J].
AIELLO, LP ;
AVERY, RL ;
ARRIGG, PG ;
KEYT, BA ;
JAMPEL, HD ;
SHAH, ST ;
PASQUALE, LR ;
THIEME, H ;
IWAMOTO, MA ;
PARK, JE ;
NGUYEN, HV ;
AIELLO, LM ;
FERRARA, N ;
KING, GL .
NEW ENGLAND JOURNAL OF MEDICINE, 1994, 331 (22) :1480-1487
[2]   SPARC paucity alleviates superoxide-mediated oxidative stress, apoptosis, and autophagy in diabetogenic hepatocytes [J].
Aseer, Kanikkai Raja ;
Silvester, Allwin Jennifa ;
Kumar, Anuj ;
Choi, Myung-Sook ;
Yun, Jong Won .
FREE RADICAL BIOLOGY AND MEDICINE, 2017, 108 :874-895
[3]   SPARC is required for the maintenance of glucose homeostasis and insulin secretion in mice [J].
Atorrasagasti, Catalina ;
Onorato, Agostina ;
Gimeno, Maria L. ;
Andreone, Luz ;
Garcia, Mariana ;
Malvicini, Mariana ;
Fiore, Esteban ;
Bayo, Juan ;
Perone, Marcelo J. ;
Mazzolini, Guillermo D. .
CLINICAL SCIENCE, 2019, 133 (02) :351-365
[4]   SPARC is a key mediator of TGF-β-induced renal cancer metastasis [J].
Bao, Ji-Ming ;
Dang, Qiang ;
Lin, Chun-Jung ;
Lo, U-Ging ;
Feldkoren, Boris ;
Dang, Andrew ;
Hernandez, Elizabeth ;
Li, Fei ;
Panwar, Vandana ;
Lee, Cheng-Fan ;
Cen, Jun-Jie ;
Guan, Bing ;
Margulis, Vitaly ;
Kapur, Payal ;
Brekken, Rolf A. ;
Luo, Jun-Hang ;
Hsieh, Jer-Tsong ;
Tan, Wan-Long .
JOURNAL OF CELLULAR PHYSIOLOGY, 2021, 236 (03) :1926-1938
[5]   In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy [J].
Becker, Kolja ;
Klein, Holger ;
Simon, Eric ;
Viollet, Coralie ;
Haslinger, Christian ;
Leparc, German ;
Schultheis, Christian ;
Chong, Victor ;
Kuehn, Markus H. ;
Fernandez-Albert, Francesc ;
Bakker, Remko A. .
SCIENTIFIC REPORTS, 2021, 11 (01)
[6]   In-Depth Molecular Characterization of Neovascular Membranes Suggests a Role for Hyalocyte-to-Myofibroblast Transdifferentiation in Proliferative Diabetic Retinopathy [J].
Boneva, Stefaniya Konstantinova ;
Wolf, Julian ;
Hajdu, Rozina Ida ;
Prinz, Gabriele ;
Salie, Henrike ;
Schlecht, Anja ;
Killmer, Saskia ;
Laich, Yannik ;
Faatz, Henrik ;
Lommatzsch, Albrecht ;
Busch, Martin ;
Bucher, Felicitas ;
Stahl, Andreas ;
Bohringer, Daniel ;
Bengsch, Bertram ;
Schlunck, Guenther ;
Agostini, Hansjurgen ;
Lange, Clemens A. K. .
FRONTIERS IN IMMUNOLOGY, 2021, 12
[7]  
Brekken Rolf A., 2001, Matrix Biology, V19, P816
[8]   The key role of proinflammatory cytokines, matrix proteins, RANKL/OPG and Wnt/β-catenin in bone healing of hip arthroplasty patients [J].
Cassuto, Jean ;
Folestad, Agnetha ;
Gothlin, Jan ;
Malchau, Henrik ;
Karrholm, Johan .
BONE, 2018, 107 :66-77
[9]   Regulation of Vascular Endothelial Growth Factor Expression by Extra Domain B Segment of Fibronectin in Endothelial Cells [J].
Chen, Shali ;
Chakrabarti, Rana ;
Keats, Emily C. ;
Chen, Megan ;
Chakrabarti, Subrata ;
Khan, Zia A. .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2012, 53 (13) :8333-8343
[10]   Glucose affects cell viability, migration, angiogenesis and cellular adhesion of human retinal capillary endothelial cells via SPARC [J].
Fu, Yang ;
Tang, Min ;
Xiang, Xiaoqiong ;
Liu, Kun ;
Xu, Xun .
EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2019, 17 (01) :273-283