Abstract
The etiology of pterygium remains unclear, but ultraviolet (UV) radiation is generally considered to be major risk factor. Pterygium has similarity features with many cancers, including inflammation, invasion, cell proliferation, anti-apoptosis, angiogenesis and recurrence after resection. Retinoic acid via cellular retinoic acid binding protein 2 (CRABP2) is involved in cell cycle arrest, apoptosis and differentiation, while it via fatty acid binding protein 5 (FABP5) is involved in survival, cell proliferation and angiogenesis, which pathway gets activated depends on the CRABP2/FABP5 ratio. Alterations of retinoid signaling were found in many cancer types. The deregulated retinoid signaling may also contribute to the development and/or recurrence of pterygium. The aim of our study was to determine mRNA and protein expressions of CRABP2 and FABP5 and ratio of CRABP2/FABP5 in primer and recurrent pterygium tissues. Pterygia tissues were collected from 30 eyes of 30 patients undergoing pterygium excision. CRABP2 and FABP5 mRNA and protein expression were assessed using Real-time PCR and Western blotting through examination of excised specimens from pterygium and conjunctiva tissues. The ratio of CRABP2/FABP5 gene expression was not altered when primary pterygium tissues compared normal conjunctival tissues (1.00-fold change). Whereas the ratio of CRABP2/ FABP5 gene expression was decreased when recurrent pterygium tissues compared normal conjunctival tissues (0.81-fold change). Understanding etiopathogenesis of pterygium may aid in the find of more promising treatments to prevent pterygium in earlier stages.
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References
Cárdenas-Cantú E, Zavala J, Valenzuela J, Valdez-García JE (2014) Molecular basis of pterygium development. Semin Ophthalmol. https://doi.org/10.3109/08820538.2014.971822
Riau AK, Wong TT, Finger SN, Chaurasia SS, Hou AH, Chen S, Yu SJ, Tong L (2011) Aberrant DNA methylation of matrix remodeling and cell adhesion related genes in pterygium. PLoS ONE 6(2):e14687. https://doi.org/10.1371/journal.pone.0014687
Houa A, Voorhoeve PM, Lana W, Tina M, Tong L (2013) Comparison of gene expression profiles in primary and immortalized human pterygium fibroblast cells. Exp Cell Res 319:2781–2789
Pérez-Rico C, Pascual G, Sotomayor S, Asúnsolo A, Cifuentes A, García-Honduvilla N, Buján J (2014) Elastin development-associated extracellular matrix constituents of subepithelial connective tissue in human pterygium. Invest Ophthalmol Vis Sci 55:6309–6318
Girolamo ND, Wakefield D, Coroneo MT (2006) UVB-Mediated induction of cytokines and growth factors in pterygium epithelial cells involves cell surface receptors and intracellular signaling. Invest Ophthalmol Vis Sci 47:2430–2437
Sha X, Liu Z, Song L, Peng J, Xie L (2014) Inhibition of a-smooth muscle actin expression and migration of pterygium fibroblasts by coculture with amniotic mesenchymal stem cells. Curr Eye Res 39:1081
Kim KW, Park SH, Wee SW, Kim JC (2013) Overexpression of angiogeninin pterygium body fibroblasts and its association with proliferative potency. Invest Ophthalmol Vis Sci 54:6355–6362
Wolf G (2008) Retinoic acid as cause of cell proliferation or cell growth inhibition depending on activation of one of two different nuclear receptors. Nutr Rev 66(1):55–59
Zhang W, Levi L, Banerjee P, Jain M, Noy N (2015) Kruppel-like factor 2 suppresses mammary carcinoma growth by regulating retinoic acid signaling. Oncotarget 6(34):35830
Collins CA, Watt FM (2008) Dynamic regulation of retinoic acid-binding proteins in developing, adult and neoplastic skin reveals roles for β-catenin and Notch signaling. Dev Biol 324:55–67
Garattini E, Bolis M, Garattini SK, Fratelli M, Centritto F, Paroni G, Gianni M, Zanetti A, Pagani A, Fisher JN et al (2014) Retinoids and breast cancer: from basic studies to the clinic and back again. Cancer Treat Rev 40:739–749
Pan L, Xiao H, Liao R, Chen Q, Peng C, Zhang Y, Mu T, Wu Z (2018) Fatty acid binding protein 5 promotes tumor angiogenesis and activates the IL6/STAT3/VEGFA pathway in hepatocellular carcinoma. Biomed Pharmacother 106:68–76
Adamson J, Morgan EA, Beesley C, Mei Y, Foster CS, Fuijii H, Rudland PS, Smith PH, Ke Y (2003) High-level expression of cutaneous fatty acid-binding protein in prostatic carcinomas and its effect on tumorigenicity. Oncogene 22(18):2739–2749. https://doi.org/10.1038/sj.onc.1206341
Feng X, Zhang M, Wang B, Zhou C, Mu Y, Li J, Liu X, Wang Y, Song Z, Liu P (2019) CRABP2 regulates invasion and metastasis of breast cancer through hippo pathway dependent on ER status. J Exp Clin Cancer Res 38(1):361
Boehm MD, Huang AJW (2004) Treatment of recurrent corneal and conjunctival intraepithelial neoplasia with topical interferon alfa 2b. Ophthalmology 111(9):1755–1761
Herbort CP, Zografos L, Zwingli M, Schoeneich M (1988) Topical retinoic acid in dysplastic and metaplastic keratinization of corneoconjunctival epithelium. Graefes Arch Clin Exp Ophthalmol 226(1):22–26
Coyle KM, Sultan M, Thomas ML, Vaghar-Kashani A, Marcato P (2013) Retinoid signaling in cancer and its promise for therapy. J Carcinog Mutagen. https://doi.org/10.4172/2157-2518.S7-006
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitave PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408
Gum SI, Kim YH, Jung JC, Kim IG, Lee JS, Lee KW, Park YJ (2017) Cyclosporine A inhibits TGF-β2- induced myofibroblast of primary cultured human pterygium fibroblasts. Biochem Biophys Res Commun 482(4):1148–1153
Chien KH, Chen SJ, Liu JH, Woung LC, Chen JT, Liang CM, Chiou SH, Tsai CY, Cheng CK, Hu CC et al (2013) Correlation of MicroRNA-145 levels and clinical severity of pterygia. Ocular Surf 11(2):133–138
Barbus S, Tews B, Karra D, Hahn M, Radlwimmer B, Delhomme N, Hartmann C, Felsberg J, Krex D, Schackert G et al (2011) (2011) Differential retinoic acid signaling in tumors of long- and short-term glioblastoma survivors. J Natl Cancer Inst 103(7):598
Dua HS, Azuara-Blanco A (2000) Limbal stem cells of the corneal epithelium. Surv Ophthalmol. 44(5):415
Vreeland AC, Yu S, Levi L, Rossetto DB, Noy N (2014) Transcript stabilization by the RNA-binding protein HuR is regulated by cellular retinoic acid-binding protein 2. Mol Cell Biol. https://doi.org/10.1128/MCB.00281-14
Ohata T, Yokoo H, Kamiyama T, Fukai M, Aiyama T, Hatanaka Y, Hatanaka K, Wakayama K, Orimo T, Kakisaka T et al (2017) Fatty acid-binding protein 5 function in hepatocellular carcinoma through induction of epithelial-mesenchymal transition. Cancer Med 6(5):1049–1061
Jeong CY, Hah YS, Cho BI, Lee SM, Joo YT, Jung EJ, Jeong SH, Lee YJ, Choi SK, Ha WS et al (2012) Fatty acid-binding protein 5 promotes cell proliferation and invasion in human intrahepatic cholongiocarcinoma. Oncol rep 28(4):1283–1292
Li Q, You C, Zhou L, Sima X, Liu Z, Liu H, Xu J (2016) High fabp5 versus crabpII expression ratio in recurrent craniopharyngiomas: ımplications for future treatment. World Neurosurg 94:197–205
Acknowledgements
The authors thank Selim DEMİR and Helin DENİZ DEMİR for their help in obtaining the patient’s samples.
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This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) 1001 (Grant Number: 215S692).
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Concept: SDC, OA; Data Collection and/or Processing: SDC, OA; Interpretation: SDC, OA; Genetic analyzing: SDC, OA; Literature Review: SDC; Writer: SDC; Critical Review: SDC, OA. The authors thank Selim DEMİR and Helin DENİZ DEMİR for their help in obtaining the patient’s samples.
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Celik, S.D., Ates, O. Analysis of CRABP2 and FABP5 genes in primary and recurrent pterygium tissues. Mol Biol Rep 47, 6105–6110 (2020). https://doi.org/10.1007/s11033-020-05686-y
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DOI: https://doi.org/10.1007/s11033-020-05686-y