https://doi.org/10.4081/ejh.2023.3663
Sodium hyaluronate promotes proliferation, autophagy, and migration of corneal epithelial cells by downregulating miR-18a in the course of corneal epithelial injury
Submitted: 31 January 2023
Accepted: 27 May 2023
Published: 15 June 2023
Accepted: 27 May 2023
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Supplementary: 61
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Corneal epithelium can resist the invasion of external pathogenic factors to protect the eye from external pathogens. Sodium hyaluronate (SH) has been confirmed to promote corneal epithelial wound healing. However, the mechanism by which SH protects against corneal epithelial injury (CEI) is not fully understood. CEI model mice were made by scratching the mouse corneal epithelium, and in vitro model of CEI were constructed via curettage of corneal epithelium or ultraviolet radiation. The pathologic structure and level of connective tissue growth factor (CTGF) expression were confirmed by Hematoxylin and Eosin staining and immunohistochemistry. CTGF expression was detected by an IHC assay. The levels of CTGF, TGF-β, COLA1A, FN, LC3B, Beclin1, and P62 expression were monitored by RT-qPCR, ELISA, Western blotting or immunofluorescence staining. Cell proliferation was detected by the CCK-8 assay and EdU staining. Our results showed that SH could markedly upregulate CTGF expression and downregulate miR-18a expression in the CEI model mice. Additionally, SH could attenuate corneal epithelial tissue injury, and enhance the cell proliferation and autophagy pathways in the CEI model mice. Meanwhile, overexpression of miR-18a reversed the effect of SHs on cell proliferation and autophagy in CEI model mice. Moreover, our data showed that SH could induce the proliferation, autophagy, and migration of CEI model cells by downregulating miR-18a. Down-regulation of miR-18a plays a significant role in the ability of SH to promote corneal epithelial wound healing. Our results provide a theoretical basis for targeting miR-18a to promote corneal wound healing.
Ljubimov AV, Saghizadeh M. Progress in corneal wound healing. Prog Retin Eye Res 2015; 49:17-45.
DOI: https://doi.org/10.1016/j.preteyeres.2015.07.002
Wilson SE, Torricelli AAM, Marino GK. Corneal epithelial basement membrane: Structure, function and regeneration. Exp Eye Res 2020;194:108002.
DOI: https://doi.org/10.1016/j.exer.2020.108002
Ma X, Wang Q, Song F, Li Y, Li J, Dou S, et al. Corneal epithelial injury-induced norepinephrine promotes Pseudomonas aeruginosa keratitis. Exp Eye Res 2020;195:108048.
DOI: https://doi.org/10.1016/j.exer.2020.108048
Raghunathan VK, Thomasy SM, Strøm P, Yañez-Soto B, Garland SP, Sermeno J, et al. Tissue and cellular biomechanics during corneal wound injury and repair. Acta Biomater 2017; 58:291-301.
DOI: https://doi.org/10.1016/j.actbio.2017.05.051
Chen W, Shi XL, He XH, Mao YH, Li C, Dong N. Loteprednol combined with sodium hyaluronate in the treatment of dry eye disease and its effect on TNF-α and CXCL10 in tears. J Biol Regul Homeost Agents 2020;34:1825-9.
Becker LC, Bergfeld WF, Belsito DV, Klaassen CD, Marks JG Jr., Shank RC, et al. Final report of the safety assessment of hyaluronic acid, potassium hyaluronate, and sodium hyaluronate. Int J Toxicol 2009;28:5-67.
DOI: https://doi.org/10.1177/1091581809337738
Wen Y, Zhang X, Chen M, Han D. Sodium hyaluronate in the treatment of dry eye after cataract surgery: a meta-analysis. Ann Palliat Med 2020;9:927-39.
DOI: https://doi.org/10.21037/apm-20-695
Carracedo G, Villa-Collar C, Martin-Gil A, Serramito M, Santamaría L. Comparison between viscous teardrops and saline solution to fill orthokeratology contact lenses before overnight wear. Eye Contact Lens 2018;44:S307-11.
DOI: https://doi.org/10.1097/ICL.0000000000000416
Camillieri G, Bucolo C, Rossi S, Drago F. Hyaluronan-induced stimulation of corneal wound healing is a pure pharmacological effect. J Ocul Pharmacol Ther 2004;20:548-553.
DOI: https://doi.org/10.1089/jop.2004.20.548
Gumusoglu E, Tuba G, Hosseini MK, Seymen N, Senol T, Sezerman U, et al. The importance of dysregulated miRNAs on ovarian cysts and epithelial ovarian cancer. Eur J Gynaecol Oncol 2021;42:66-72.
DOI: https://doi.org/10.31083/j.ejgo.2021.01.2167
Saliminejad K, Khorram Khorshid HR, Soleymani Fard S, Ghaffari SH. An overview of microRNAs: Biology, functions, therapeutics, and analysis methods. J Cell Physiol 2019;234:5451-65.
DOI: https://doi.org/10.1002/jcp.27486
Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol 2018;141:1202-7.
DOI: https://doi.org/10.1016/j.jaci.2017.08.034
Mohr AM, Mott JL. Overview of microRNA biology. Semin Liver Dis 2015;35:3-11.
DOI: https://doi.org/10.1055/s-0034-1397344
Garofalo M, Leva GD, Croce CM. MicroRNAs as anti-cancer therapy. Curr Pharm Des 2014;20:5328-35
DOI: https://doi.org/10.2174/1381612820666140128211346
Kalayinia S, Arjmand F, Maleki M, Malakootian M, Singh CP. MicroRNAs: roles in cardiovascular development and disease. Cardiovasc Pathol 2021;50:107296.
DOI: https://doi.org/10.1016/j.carpath.2020.107296
Lee SK, Teng Y, Wong HK, Ng TK, Huang L, Lei P, et al. MicroRNA-145 regulates human corneal epithelial differentiation. PLoS One 2011;6:e21249.
DOI: https://doi.org/10.1371/journal.pone.0021249
Zhang X, Di G, Dong M, Qu M, Zhao X, Duan H, et al. Epithelium-derived miR-204 inhibits corneal neovascularization. Exp Eye Res 2018;167:122-7.
DOI: https://doi.org/10.1016/j.exer.2017.12.001
Cao Q, Xu W, Chen W, Peng D, Liu Q, Dong J, et al. MicroRNA-184 negatively regulates corneal epithelial wound healing via targeting CDC25A, CARM1, and LASP1. Eye Vis (Lond) 2020;7:35.
DOI: https://doi.org/10.1186/s40662-020-00202-6
Fu JY, Yu XF, Wang HQ, Lan JW, Shao WQ, Huo YN. MiR-205-3p protects human corneal epithelial cells from ultraviolet damage by inhibiting autophagy via targeting TLR4/NF-κB signaling. Eur Rev Med Pharmacol Sci 2020;24:6494-504.
Wang F, Wang D, Song M, Zhou Q, Liao R, Wang Y. MiRNA-155-5p reduces corneal epithelial permeability by remodeling epithelial tight junctions during corneal wound healing. Curr Eye Res 2020; 45:904-13.
DOI: https://doi.org/10.1080/02713683.2019.1707229
Zhang Y, Yuan F, Liu L, Chen Z, Ma X, Lin Z, et al. The role of the miR-21/SPRY2 axis in modulating proangiogenic factors, epithelial phenotypes, and wound healing in corneal epithelial cells. Invest Ophthalmol Vis Sci 2019;60:3854-62.
DOI: https://doi.org/10.1167/iovs.19-27013
Nair MG, Prabhu JS, Korlimarla A, Rajarajan S, P SH, Kaul R, et al. miR-18a activates Wnt pathway in ER-positive breast cancer and is associated with poor prognosis. Cancer Med 2020;9:5587-97.
DOI: https://doi.org/10.1002/cam4.3183
Zhang L, Kong L, Yang Y. miR-18a Inhibitor suppresses leukemia cell proliferation by upregulation of PTEN expression. Med Sci Monit 2020;26:e921288.
DOI: https://doi.org/10.12659/MSM.921288
Qi B, Dong Y, Qiao XL. Effects of miR-18a on proliferation and apoptosis of gastric cancer cells by regulating RUNX1. Eur Rev Med Pharmacol Sci 2020;24:9957-64.
Humphreys KJ, McKinnon RA, Michael MZ. miR-18a inhibits CDC42 and plays a tumour suppressor role in colorectal cancer cells. PLoS One 2014;9:e112288.
DOI: https://doi.org/10.1371/journal.pone.0112288
Yu H, Yu Y, Zhao Z, Cui L, Hou J, Shi H. Prdx6 is required to protect human corneal epithelial cells against ultraviolet B injury. Eur J Ophthalmol 2021;31:367-78.
DOI: https://doi.org/10.1177/1120672119896426
Xu M, Sivak JG, McCanna DJ. Ocular toxicology: synergism of UV radiation and benzalkonium chloride. Cutan Ocul Toxicol 2020;39:370-9.
DOI: https://doi.org/10.1080/15569527.2020.1833027
Agrawal VB, Tsai RJ. Corneal epithelial wound healing. Indian J Ophthalmol 2003;51:5-15.
Wilson SE. Corneal wound healing. Exp Eye Res 2020;197:108089.
DOI: https://doi.org/10.1016/j.exer.2020.108089
Asena L, Gökgöz G, Helvacıoğlu F, Özgün G, Deniz EE, Dursun Altinors D. Effects of topical coenzyme Q10, Xanthan gum and sodium hyaluronate on corneal epithelial wound healing. Clin Exp Optom 2022;105:378-84.
DOI: https://doi.org/10.1080/08164622.2021.1932433
Ozek D, Kemer OE. Effect of the bioprotectant agent trehalose on corneal epithelial healing after corneal cross-linking for keratoconus. Arq Bras Oftalmol 2018;81:505-9.
DOI: https://doi.org/10.5935/0004-2749.20180100
Mohamed YH, Uematsu M, Ueki R, Inoue D, Sasaki H, Kitaoka T. Safety of sodium hyaluronate eye drop with C12-benzalkonium chloride. Cutan Ocul Toxicol 2019;38:156-60.
DOI: https://doi.org/10.1080/15569527.2018.1543316
Gomes JA, Amankwah R, Powell-Richards A, Dua HS. Sodium hyaluronate (hyaluronic acid) promotes migration of human corneal epithelial cells in vitro. Br J Ophthalmol 2004;88:821-5.
DOI: https://doi.org/10.1136/bjo.2003.027573
Mi Y, Miao Q, Cui J, Tan W, Guo Z. Novel 2-Hydroxypropyltrimethyl ammonium chitosan derivatives: synthesis, characterization, moisture absorption and retention properties. Molecules 2021;26:4238.
DOI: https://doi.org/10.3390/molecules26144238
Lee JS, Park JM, Cho HK, Kim SJ, Huh HD, Park YM. Influence of sodium hyaluronate concentration on corneal aberrations in soft contact lens wearers. Korean J Ophthalmol 2018;32:89-94.
DOI: https://doi.org/10.3341/kjo.2017.0099
Bock U, Deylen DV, Jochner M, Doerr M, Stäbler C, Reichl S. Development of in vitro methodologies to investigate binding by sodium hyaluronate in eye drops to corneal surfaces. Open Ophthalmol J 2018;12:226-40.
DOI: https://doi.org/10.2174/1874364101812010226
Liu CH, Huang S, Britton WR, Chen J. MicroRNAs in vascular eye diseases. Int J Mol Sci 2020;21:649.
DOI: https://doi.org/10.3390/ijms21020649
Kaplan N, Liu M, Wang J, Yang W, Fiolek E, Peng H, et al. Eph signaling is regulated by miRNA-210: Implications for corneal epithelial repair. FASEB J 2022;36:e22076.
DOI: https://doi.org/10.1096/fj.202101423R
Yang Y, Gong B, Wu ZZ, Shuai P, Li DF, Liu LL, et al. Inhibition of microRNA-129-5p expression ameliorates ultraviolet ray-induced corneal epithelial cell injury via upregulation of EGFR. J Cell Physiol 2019;234:11692-707.
DOI: https://doi.org/10.1002/jcp.27837
Guo Y, Lu X, Wang H. Downregulation of miR-18a induces CTGF and promotes proliferation and migration of sodium hyaluronate treated human corneal epithelial cells. Gene 2016 591:129-36.
DOI: https://doi.org/10.1016/j.gene.2016.07.008
Chen J, Wang J, Wu X, Simon N, Svensson CI, Yuan J, et al. eEF2 improves dense connective tissue repair and healing outcome by regulating cellular death, autophagy, apoptosis, proliferation and migration. Cell Mol Life Sci 2023;80:128.
DOI: https://doi.org/10.1007/s00018-023-04776-x
Wei C, Pan Y, Zhang Y, Dai Y, Jiang L, Shi L, et al. Overactivated sonic hedgehog signaling aggravates intrauterine adhesion via inhibiting autophagy in endometrial stromal cells. Cell Death Dis 2020;11:935.
DOI: https://doi.org/10.1038/s41419-020-03128-y
Ma F, Li R, Tang H, Zhu T, Xu F, Zhu J. Regulation of autophagy in mesenchymal stem cells modulates therapeutic effects on spinal cord injury. Brain Res 2019;1721:146321.
DOI: https://doi.org/10.1016/j.brainres.2019.146321
Kim E, Ham S, Jung BK, Park JW, Kim J, Lee JH. Effect of baicalin on wound healing in a mouse model of pressure ulcers. Int J Mol Sci 2022;24:329.
DOI: https://doi.org/10.3390/ijms24010329
Liarte S, Bernabé-García Á, Rodríguez-Valiente M, Moraleda JM, Castellanos G, Nicolás FJ. Amniotic Membrane restores chronic wound features to normal in a keratinocyte TGF-β-chronified cell model. Int J Mol Sci 2023;24:6210.
DOI: https://doi.org/10.3390/ijms24076210
Laursen SH, Hansen SG, Taskin MB, Chen M, Wogensen L, Nygaard JV, et al. Electrospun nanofiber mesh with connective tissue growth factor and mesenchymal stem cells for pelvic floor repair: Long-term study. J Biomed Mater Res B Appl Biomater 2023;111:392-401.
DOI: https://doi.org/10.1002/jbm.b.35158
Jiang K, Li Y, Xiang C, Xiong Y, Jia J. Rebalancing SMAD7/SMAD3 signaling reduces adhesion formation during flexor tendon healing. J Microbiol Biotechnol 2023;33:339-47.
DOI: https://doi.org/10.4014/jmb.2209.09033
Blalock TD, Duncan MR, Varela JC, Goldstein MH, Tuli SS, Grotendorst GR, et al. Connective tissue growth factor expression and action in human corneal fibroblast cultures and rat corneas after photorefractive keratectomy. Invest Ophthalmol Vis Sci 2003;44:1879-87.
DOI: https://doi.org/10.1167/iovs.02-0860
Ethics Approval
Ethical approval was obtained for all experimental procedures by the Ethics Committee of the Hunan Provincial People's HospitalSupporting Agencies
Natural Science Foundation of Hunan Province of China, Ren Shu Foundation of Hunan Provincial People's Hospital, Research and Development Program in Key areas of Hunan Province, Department of Education of Hunan ProvinceHow to Cite
Guo, Y., & Wang, H. (2023). Sodium hyaluronate promotes proliferation, autophagy, and migration of corneal epithelial cells by downregulating miR-18a in the course of corneal epithelial injury. European Journal of Histochemistry, 67(2). https://doi.org/10.4081/ejh.2023.3663
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