Lithium chloride (LiCl) induced autophagy and downregulated expression of transforming growth factor β-induced protein (TGFBI) in granular corneal dystrophy.

Author(s) Nie, D.; Peng, Y.; Li, M.; Liu, X.; Zhu, M.; Ye, L.
Journal Exp Eye Res
Date Published 2018 Apr 18
Abstract

This study evaluated whether lithium chloride (LiCl) prevents cytoplasmic accumulation of mutant-transforming growth factor β-induced protein (Mut-TGFBI) in granular corneal dystrophy (GCD) via activation of the autophagy pathway. Levels of TGFBI and microtubule-associated protein 1A/1B-light chain 3 (LC3) in 3 GCD patients and healthy controls were analyzed by immunohistochemistry (IHC) staining and Western blot. Primary corneal fibroblasts were isolated and transfected with wild type or mutant type TGFBI over-expressed vectors, and then treated with LiCl and/or autophagy inhibitor 3-methyladenine (3-MA). Then, levels of TGFBI, glycogen synthase kinase-3 (GSK-3) and LC3-I/-II were detected. Cell viability and transmission electron microscopy assay were also performed. Levels of TGFBI and LC3 were significantly increased in GCD patients. Over-expression of mutant type TGFBI inhibited cell viability and induced autophagy in corneal fibroblasts. LiCl downregulated the expression of TGFBI in mutant type TGFBI over-expressed cells in a dose- and time-dependent manner. LiCl enhanced autophagy in mutant type TGFBI over-expressed cells and recovered cell viability in those cells. However, the effects of LiCl were partly attenuated when autophagy was suppressed by 3-MA. To summarize, treatment with LiCl inhibited the expression of TGFBI and recovery the inhibitory of mutant type TGFBI in cell viability, at least part through enhancing of autophagy. These data strongly suggest that LiCl may be useful in the treatment of GCD.

DOI 10.1016/j.exer.2018.04.008
ISSN 1096-0007
Citation Nie D, Peng Y, Li M, Liu X, Zhu M, Ye L. Lithium chloride (LiCl) induced autophagy and downregulated expression of transforming growth factor β-induced protein (TGFBI) in granular corneal dystrophy. Exp Eye Res. 2018.

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