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

Nie, Danyao; Peng, Yun; Li, Ming; Liu, Xinhua; Zhu, Meilan; Lin, Yun Fei

doi:10.1016/j.exer.2018.04.008

Cited by 13 publications

(6 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accumulating data also indicate that lithium promotes recovery from injury in many organs. For example, lithium is able to protect against liver ischemia/reperfusion injury in rats, bronchopulmonary dysplasia in newborn rats sustaining hyperoxia, and granular corneal dystrophy in animal models (52‐54). In all of these studies, a proautophagic effect was consistently found to contribute to the beneficial action of lithium treatment.…”

Section: Discussionmentioning

confidence: 99%

Lithium targeting of AMPK protects against cisplatin‐induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells

et al. 2019

View full text Add to dashboard Cite

Autophagy has been demonstrated to be vital for kidney homeostasis and is centrally implicated in the pathogenesis of cisplatin-induced acute kidney injury (AKI). Lithium is a potent autophagy inducer in a number of cell types. However, it remains uncertain whether its autophagic activity is associated with a beneficial effect on renal tubular cells in AKI. This study aimed to examine the effect of lithium on renal autophagy in cisplatin-induced AKI. Mice or renal proximal tubular epithelial cells in culture were exposed to cisplatin-induced acute injury in the presence or absence of lithium treatment. AKI or tubular cell injury was evaluated, and cell signaling associated with autophagy was examined. Lithium pretreatment prominently ameliorated acute renal tubular damage in mice exposed to cisplatin insult, associated with enhanced autophagy in renal tubules, as assessed by measuring microtubule-associated protein 1A/1B-light chain 3 (LC3)BII/I expression and autophagosome formation. Consistently, in cisplatin-injured renal tubular cells in vitro, lithium enhanced autophagic activities, improved cell viability, and attenuated cell death. Mechanistically, lithium triggered AMPK-a phosphorylation and activation, which in turn positively correlated with the induced expression of autophagy-related molecules, like mammalian target of rapamycin and LC3BII/I. AMPK-a activation is likely required for lithium-induced tubular cell autophagy and protection in cisplatin-induced AKI because blockade of AMPK-a phosphorylation by compound C markedly abrogated lithium-induced autophagosome formation and mitigated the protective effect of lithium on AKI. Our findings suggest that lithium represents a promising therapeutic strategy for protecting renal tubular cells against cisplatin-induced AKI by enhancing autophagy via AMPK-a activation.

show abstract

Section: Discussionmentioning

confidence: 99%

Lithium targeting of AMPK protects against cisplatin‐induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells

et al. 2019

View full text Add to dashboard Cite

show abstract

“…It has been established that acridine orange accumulates in acidic organelles 20 . Cells were cultured on a cover glass slide chamber, followed by the designated treatments.…”

Section: Methodsmentioning

confidence: 99%

“…It has been established that acridine orange accumulates in acidic organelles. 20 Cells were cultured on a cover glass slide chamber, followed by the designated treatments. Briefly, corneal fibroblasts were exposed to 0.5 μg/mL acridine orange (Sigma-Aldrich) for 15 minutes at 37°C.…”

Section: Acridine Orange Stainingmentioning

confidence: 99%

Lysosomal dysfunction of corneal fibroblasts underlies the pathogenesis of Granular Corneal Dystrophy Type 2 and can be rescued by TFEB

Choi

Woo

Kim

2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

Granular corneal dystrophy type 2 (GCD2) is the most common form of transforming growth factor β‐induced (TGFBI) gene‐linked corneal dystrophy and is pathologically characterized by the corneal deposition of mutant‐TGFBIp. The defective autophagic degradation of pathogenic mutant‐TGFBIp has been shown in GCD2; however, its exact mechanisms are unknown. To address this, we investigated lysosomal functions using corneal fibroblasts. Levels of cathepsins K and L (CTSK and CTSL) were significantly decreased in GCD2 cells, but of cathepsins B and D (CTSB and CTSD) did not change. The maturation of the pro‐enzymes to their active forms (CTSB, CTSK and CTSL) was inhibited in GCD2 cells. CTSL enzymes directly degraded both LC3 (autophagosomes marker) and mutant‐TGFBIp. Exogenous CTSL expression dramatically reduced mutant‐TGFBIp in GCD2 cells, but not TGFBIp in WT cells. An increased lysosomal pH and clustered lysosomal perinuclear position were found in GCD2 cells. Transcription factor EB (TFEB) levels were significantly reduced in GCD2 cells, compared to WT. Notably, exogenous TFEB expression improved mutant‐TGFBIp clearance and lysosomal abnormalities in GCD2 cells. Taken together, lysosomal dysfunction in the corneal fibroblasts underlies the pathogenesis of GCD2, and TFEB has a therapeutic potential in the treatment of GCD2.

show abstract

“…The effect was more obvious with the cotreatment of melatonin and rapamycin [ 85 ]. Lithium chloride (LiCl) increased autophagy in Mu TGFBI-overexpressing cells, inhibited the negative effects and partly recovered the cell viability in GCD [ 86 ]. Autophagy was triggered and autophagic flux was impaired in keratocytes of macular corneal dystrophy (Groenouw II type CD), which is a rare autosomal recessive-inherited condition characterized by progressive loss of vision, photophobia, and discomfort on the ocular surface [ 87 ].In the cornea of Slc4a11 knock out mouse model, mitochondrial ROS disrupted TFEB signaling causing impairment of autophagy and congenital hereditary endothelial dystrophy [ 88 ].…”

Section: Research Progress Of Exosomes and Autophagy In Ocular Surfac...mentioning

confidence: 99%

Exosomes and autophagy in ocular surface and retinal diseases: new insights into pathophysiology and treatment

Liu

Yin

et al. 2022

Stem Cell Res Ther

View full text Add to dashboard Cite

Background Ocular surface and retinal diseases are widespread problems that cannot be ignored in today’s society. However, existing prevention and treatment still have many shortcomings and limitations, and fail to effectively hinder the occurrence and development of them. Main body The purpose of this review is to give a detailed description of the potential mechanism of exosomes and autophagy. The eukaryotic endomembrane system refers to a range of membrane-bound organelles in the cytoplasm that are interconnected structurally and functionally, which regionalize and functionalize the cytoplasm to meet the needs of cells under different conditions. Exosomal biogenesis and autophagy are two important components of this system and are connected by lysosomal pathways. Exosomes are extracellular vesicles that contain multiple signaling molecules produced by multivesicular bodies derived from endosomes. Autophagy includes lysosome-dependent degradation and recycling pathways of cells or organelles. Recent studies have revealed that there is a common molecular mechanism between exosomes and autophagy, which have been, respectively, confirmed to involve in ocular surface and retinal diseases. Conclusion The relationship between exosomes and autophagy and is mostly focused on fundus diseases, while a deeper understanding of them will provide new directions for the pathological mechanism, diagnosis, and treatment of ocular surface and retinal diseases.

show abstract

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

Cited by 13 publications

References 28 publications

Lithium targeting of AMPK protects against cisplatin‐induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells

Lithium targeting of AMPK protects against cisplatin‐induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells

Lysosomal dysfunction of corneal fibroblasts underlies the pathogenesis of Granular Corneal Dystrophy Type 2 and can be rescued by TFEB

Exosomes and autophagy in ocular surface and retinal diseases: new insights into pathophysiology and treatment

Contact Info

Product

Resources

About