Document Type : Original Article
Authors
- Elnaz Taghvaei-Bijandi 1
- Fatemeh Abedian 1
- Ahmad Ahmadzadeh Amiri 2
- Narjes Jafari 1
- Saeid Abediankenari 1
1 Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
2 Department of Ophthalmology, Mazandaran University of Medical Sciences, Sari, Iran.
Abstract
Background: Retinopathy of diabetes is a chronic diabetes mellitus complication affecting retinal vessels, and some ocular complications’ molecular mechanisms remain obscure.
Objective: To evaluate the expression of HLA-G1, HLA-G5, miRNA-181a, and miRNA-34a in the lens epithelial cells of patients with retinopathy of diabetes.
Methods: In a case-control study, 30 diabetic patients with retinopathy, 30 diabetic patients without retinopathy, and 30 cataract patients without diabetes mellitus as the control group were enrolled after a full description with details about the study methods and objectives. The expression of HLA G1, HLA G5, miRNA-181a, and miRNA-34a in lens epithelial cells was assessed by quantitative RT PCR. Moreover, the levels of HLA-G protein in aqueous humor were evaluated by the ELISA method.
Results: HLA-G1 expression was significantly upregulated in the retinopathy group (P=0.003). The aqueous humor of diabetic retinopathy patients contained significantly higher levels of HLA-G protein compared with the non-diabetic patients (P=0.001). miRNA-181a was significantly downregulated in the diabetic retinopathy group compared with the patients without diabetes (P=0.001). In addition, miRNA-34a was upregulated in the retinopathy group (P=0.009).
Conclusion: Taken together, the present results showed that HLA-G1 and miRNA-34a can be valuable markers for diabetic retinopathy. Our data offers new perspectives for improving the control of inflammation in the lens epithelial cells by considering HLA-G and miRNA.
Keywords
- Cade WT. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther. 2008;88(11):1322-1335
- Fong DS, Aiello L, Gardner TW, King GL, Blankenship G, Cavallerano JD, et al. Retinopathy in diabetes. Diabetes care. 2004; 27:s84-s87
- Beltramo E, Porta M. Pericyte loss in diabetic retinopathy mechanisms and consequences. Curr Med Chem. 2013;20:3218-3225
- Jafari N, Abediankenari S MicroRNA-34 dysregulation in gastric cancer and gastric cancer stem cell. Tumor Biol. 2017; 39:1010428317701652.
- Dong N, Tang X, Xu B. miRNA-181a Inhibits the Proliferation, Migration, and Epithelial–Mesenchymal Transition of Lens Epithelial CellsmiRNA-181a in the Treatment of PCO. Invest Ophthalmol Vis Sci. 2015;56:993-1001.
- Fons P, Chabot S, Cartwright JE, Lenfant F, L'Faqihi F, Giustiniani J, et al. Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells. Blood. 2006; 108:2608-2615.
- Svendsen SG, Udsen MS, Daouya M, Funck T, Wu C-L, Carosella ED, et al. Expression and differential regulation of HLA-G isoforms in the retinal pigment epithelial cell line, ARPE-19. Hum Immunol. 2017; 78:414-420.
- Carosella ED, Favier B, Rouas-Freiss N, Moreau P, LeMaoult J, et al. Beyond the increasing complexity of the immunomodulatory HLA-G molecule. Blood. 2008;111:4862-4870.
- Saeideh Sadat Shobeiri , Zahra Rahmani , Hadi Hossein Nataj , Hossein Ranjbaran , Masoud Mohammadi , Saeid Abediankenari.Uterine Natural Killer Cell and Human Leukocyte Antigen-G1 and Human Leukocyte Antigen-G5 Expression in Vaginal Discharge of Threatened-Abortion Women: A Case-Control Study. J Immunol Res. 2015; 2015:692198
- Porto IO, Mendes-Junior CT, Felício LP, Georg RC, Moreau P, Donadi EA, et al. MicroRNAs targeting the immunomodulatory HLA-G gene: a new survey searching for microRNAs with potential to regulate HLA-G. Mol Immunol. 2015 ;65:230-241.
- Chen Q, Luo G, Zhang X. MiR‑148a modulates HLA‑G expression and influences tumor apoptosis in esophageal squamous cell carcinoma. Experimental and Therapeutic Medicine. 2017;14:4448-4452.
- Abediankenari S, Eslami MB, Sarrafnejad A, Mohseni M, Larijani B. Dendritic cells bearing HLA-G inhibit T-Cell activation in type 1 diabetes.Iran J Allergy Asthma Immunol. 2007;6(1):1-7.
- McGEER PL, McGEER EG. Inflammation and the degenerative diseases of aging. Ann N Y Acad Sci. 2004;1035:104-116.
- Bandello F, Lattanzio R, Zucchiatti I, Del Turco C. pathophysiology and treatment of diabetic retinopathy.Acta Diabetol. 2013;50(1):1-20.
- Le Discorde M, Moreau P, Sabatier P, et al. Expression of HLA-G in human cornea, an immune-privileged tissue. Hum immunol. 2003; 64:1039-1044.
- Rizzo R, Bortolotti D, Bolzani S, Fainardi E. HLA-G molecules in autoimmune diseases and infections. Front immunol. 2014;5:592.
- Yan W-H, Lin A, Chen B-G, Chen S-Y. Induction of both membrane-bound and soluble HLA-G expression in active human cytomegalovirus infection. J Infect Dis. 2009;200:820-826.
- Feng S, Yu H, Yu Y, Geng Y, Li D, Yang C, et al. Levels of Inflammatory Cytokines IL-1β, IL-6, IL-8, IL-17A, and TNF-α in Aqueous Humour of Patients with Diabetic Retinopathy. J Diabetes Res. 2018; 4:8546423.
- Yan D, Da Dong X, Chen X, Yao S, Wang L, Wang J, et al. Role of microRNA-182 in posterior uveal melanoma: regulation of tumor development through MITF, BCL2 and cyclin D2. PloS one. 2012;7:e40967.
- Ma J, Wang J, Liu Y, Wang C, Duan D, Lu N, et al. Comparisons of serum miRNA expression profiles in patients with diabetic retinopathy and type 2 diabetes mellitus. Clinics. 2017;72:111-115.
- Kong L, Zhu J, Han W, Jiang X, Xu M, Zhao Y, et al. Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study. Acta diabetol. 2011;48:61-69.
- Xiong F, Du X, Hu J, Li T, Du S, Wu Q. Altered retinal microRNA expression profiles in early diabetic retinopathy: an in silico analysis. Curr Eye Res. 2014; 39:720-729.
- Ramzan F, D'Souza RF, Durainayagam BR, Milan AM, Markworth JF, Miranda-Soberanis V, Sequeira IR, Roy NC, Poppitt SD, Mitchell CJ, Cameron-Smith D. Circulatory miRNA biomarkers of metabolic syndrome. Acta Diabetol. 2019; 21. doi: 10.1007/s00592-019-01406-6.
- Zhu X-m, Han T, Wang X-h, Li Y-h, Yang H-g, Luo Y-n, et al. Overexpression of miR-152 leads to reduced expression of human leukocyte antigen-G and increased natural killer cell mediated cytolysis in JEG-3 cells. Am J Obstet Gynecol. 2010;202:592 e1-592 e7.
- Ragab HM, Ezzat WM, Hassan EM, El Maksoud NA, Afify M, Abd El-Maksoud MDE, Elaziz WA. Significance of MiRNA-34a and MiRNA-192 as a risk factor for nonalcoholic fatty liver disease. J Genet Eng Biotechnol. 2023;21(1).
- Kumar V, Pandey A, Arora A, Gautam P, Bisht D, Gupta S, Chaurasia A, Sachan M. Diagnostics and Therapeutic Potential of miR-205 and miR-34a in Ovarian Cancer Management: A miRNA-Target-Based Analysis. DNA Cell Biol. 2023 Feb 13. doi: 10.1089/dna.2022.0487.
)