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Abstract

Purpose:

Treatment of corneal injury depends on the self-proliferation ability of human corneal epithelial cells (HCEp). Our previous study revealed kojic acid had the anti-senescence function on human corneal endothelial cells. In this study, we researched the enhancive proliferation effect of kojic acid in HCEp.

Methods:

Cell viability was evaluated by MTT assay. The expression of proliferation-related protein was detected by western blotting and immunofluorescence assay.

Results:

Kojic acid could enhance HCEp proliferation, characterized by promoting cell proliferation rate, decreasing the expression levels of p21, galectin 8 and ki67, and increasing that of p-p38. The p38 signaling pathway inhibitor, SB203580, could reverse the enhancive proliferation function of kojic acid. Furthermore, knockdown of p21 had similar enhancive proliferation effect to kojic acid.

Conclusion:

Kojic acid might enhance HCEp proliferation through p38 and p21 signaling pathways, potentially via reduced expression levels of galectin 8 and ki67. Hence, kojic acid might be a potential drug to accelerate the healing of corneal epithelial injury.

Keywords

Kojic acid human corneal epithelial cells cell proliferation p21 p38

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References

Eghrari

Riazuddin

Gottsch

JD.

Overview of the cornea: structure, function, and development. Prog Mol Biol Transl Sci 2015; 134: 7–23.

Colombo-Barboza

Felberg

, et al. Induction of corneal collagen cross-linking in experimental corneal alkali burns in rabbits. Arq Bras Oftalmol 2014; 77(5): 310–314.

Iglesias-Bartolome

Patel

Cotrim

, et al. mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis. Cell Stem Cell 2012; 11(3): 401–414.

Functional role of CCCTC binding factor (CTCF) in stress-induced apoptosis. Exp Cell Res 2007; 313(14): 3057–3065.

Wang

Shell

UV-induced signaling pathways associated with corneal epithelial cell apoptosis. Invest Ophthalmol Vis Sci 2003; 44(12): 5102–5109.

Suarez-Barrio

Etxebarria

Hernaez-Moya

, et al. Hyaluronic acid combined with serum rich in growth factors in corneal epithelial defects. Int J Mol Sci 2019; 20(7): 1655.

Zhao

SZ.

Mesenchymal stem cells: potential role in corneal wound repair and transplantation. World J Stem Cells 2014; 6(3): 296–304.

Kim

Choi

EJ.

Compromised MAPK signaling in human diseases: an update. Arch Toxicol 2015; 89(6): 867–882.

Sun

Liu

, et al. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct Res 2015; 35(6): 600–604.

10.

Weng

Wang

, et al. Amiodarone induces cell proliferation and myofibroblast differentiation via ERK1/2 and p38 MAPK signaling in fibroblasts. Biomed Pharmacother 2019; 115: 108889.

11.

Tang

, et al. Tripartite motif-containing protein 7 regulates hepatocellular carcinoma cell proliferation via the DUSP6/p38 pathway. Biochem Biophys Res Commun 2019; 511(4): 889–895.

12.

Koff

Cell-cycle inhibitors: three families united by a common cause. Gene 2000; 247(1–2): 1–15.

13.

Deng

Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell 1995; 82(1): 675–684.

14.

Troncoso

Ferragut

Bacigalupo

, et al. Galectin-8: a matricellular lectin with key roles in angiogenesis. Glycobiology 2014; 24(10): 907–914.

15.

Arbel-Goren

Levy

Ronen

, et al. Cyclin-dependent kinase inhibitors and JNK act as molecular switches, regulating the choice between growth arrest and apoptosis induced by galectin-8. J Biol Chem 2005; 280(19): 19105–19114.

16.

Fabiani

Barabino

Rashid

, et al. Corneal epithelial proliferation and thickness in a mouse model of dry eye. Exp Eye Res 2009; 89(2): 166–171.

17.

Faig

Moretti

Joseph

, et al. Biodegradable kojic acid-based polymers: controlled delivery of bioactives for melanogenesis inhibition. Biomacromolecules 2016; 18(2): 363–373.

18.

Nohynek

Kirkland

Marzin

, et al. An assessment of the genotoxicity and human health risk of topical use of kojic acid [5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one]. Food Chem Toxicol 2004; 42(1): 93–105.

19.

Asadzadeh

Sirous

Pourfarzam

, et al. In vitro and in silico studies of the inhibitory effects of some novel kojic acid derivatives on tyrosinase enzyme. Iran J Basic Med Sci 2016; 19(2): 132–144.

20.

Higa

Kawabe

Nabae

, et al. Kojic acid -absence of tumor-initiating activity in rat liver, and of carcinogenic and photo-genotoxic potential in mouse skin. J Toxicol Sci 2007; 32(2): 143–159.

21.

Aytemir

Septioglu

Calis

Synthesis and anticonvulsant activity of new kojic acid derivatives. Arzneimittelforschung 2010; 60(1): 22–29.

22.

Gomes

Lunardi

Gonzalez

, et al. The antioxidant action of Polypodium leucotomos extract and kojic acid: reactions with reactive oxygen species. Braz J Med Biol Res 2001; 34(11): 1487–1494.

23.

Yoo

Lee

Choi

, et al. A modulatory effect of novel kojic acid derivatives on cancer cell proliferation and macrophage activation. Pharmazie 2010; 65(4): 261–266.

24.

Wei

Luo

Yan

, et al. Kojic acid inhibits senescence of human corneal endothelial cells via NF-kappaB and p21 signaling pathways. Exp Eye Res 2019; 180: 174–183.

25.

Yan

Qian

Jiang

, et al. Laminins in an in vitro anterior lens capsule model established using HLE B-3 cells. Mol Med Rep 2018; 17(4): 5726–5733.

26.

Mateoiu

Pirici

Bogdan

Immunohistochemical nuclear staining for p53, PCNA, Ki-67 and bcl-2 in different histologic variants of basal cell carcinoma. Rom J Morphol Embryol 2011; 52: 315–319.

Kojic acid enhances the proliferation of human corneal epithelial cells via p38 and p21 signaling pathways