Format

Send to

Choose Destination
Exp Eye Res. 2019 Mar;180:174-183. doi: 10.1016/j.exer.2018.12.020. Epub 2018 Dec 28.

Kojic acid inhibits senescence of human corneal endothelial cells via NF-κB and p21 signaling pathways.

Author information

1
Eye Hospital, First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Harbin, 150001, China; Academician Workstation, College of Pharmacy, Harbin Medical University, Heilongjiang Academy of Medical Sciences, 157 Baojian Road, Harbin, 150081, China.
2
Eye Hospital, First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Harbin, 150001, China.
3
Academician Workstation, College of Pharmacy, Harbin Medical University, Heilongjiang Academy of Medical Sciences, 157 Baojian Road, Harbin, 150081, China.
4
Eye Hospital, First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Harbin, 150001, China. Electronic address: tangxianling2007@126.com.
5
Eye Hospital, First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Harbin, 150001, China. Electronic address: liuping2017lq@163.com.

Abstract

Fuchs endothelial dystrophy (FED) and late cornea allograft failure of cornea transplantation are associated with human corneal endothelial cells (HCEC) senescence. Kojic acid has various functions, however, its anti-senescence effect has never been identified. In this study, we investigated the anti-senescence effect of kojic acid on HCEC. Cell viability, migration ability and senescence were evaluated by MTT assay, migration assay, and senescence-associated beta-galactosidase (SA-β-Gal) staining, respectively. Senescence-related protein expression was analyzed by western blotting and immunofluorescence assay. Angiogenesis of human umbilical vein endothelial cells (HUVEC) was examined by tube formation assay and spheroid sprouting assay. The results showed that kojic acid could inhibit HCEC senescence, characterized by enhancing migration, decreasing the levels of SA-β-Gal staining, galectin 8, laminin α1, laminin α2, laminin γ1 and p21, and increasing that of p-NF-κB of senescent HCEC. The p-NF-κB inhibitor could reverse the anti-senescent effect of kojic acid, and p21 siRNA showed similar anti-senescence effect with kojic acid. In addition, kojic acid could alleviate HUVEC tube formation induced by senescent HCEC, which could be reversed by p-NF-κB inhibitor. The p21 siRNA could alleviate HUVEC spheroid sprouting induced by senescent HCEC. These results indicated that kojic acid might inhibit HCEC senescence and following resulted angiogenesis via NF-κB and p21 signaling pathways, possibly through downregulation of galectin 8 and laminins. Therefore, kojic acid is a promising drug for HCEC senescence-related diseases such as FED and late cornea allograft failure.

KEYWORDS:

Angiogenesis; Galectin 8; Human corneal endothelial cells; Kojic acid; Laminin; Senescence; p-NF-κB; p21

PMID:
30597146
DOI:
10.1016/j.exer.2018.12.020
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center