Dexamethasone Downregulates Autophagy through Accelerated Turn-Over of the Ulk-1 Complex in a Trabecular Meshwork Cells Strain: Insights on Steroid-Induced Glaucoma Pathogenesis

Sbardella, Diego; Tundo, Grazia R.; Coletta, Massimo; Manni, Gianluca; Oddone, Francesco

doi:10.3390/ijms22115891

Cited by 19 publications

(7 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism of injury caused by GCs to BMECs is not clear. Sbardella et al found that dexamethasone inhibited trabecular meshwork cells by downregulating autophagy, a kind of secretory endothelial cell similar to BMECs, causing metabolic disorder and even apoptosis [27]. Under normal circumstances, autophagy is at a low level, and only moderate autophagy has a protective effect.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles from BMSCs Prevent Glucocorticoid-Induced BMECs Injury by Regulating Autophagy via the PI3K/Akt/mTOR Pathway

Shen

Yue

et al. 2022

Cells

View full text Add to dashboard Cite

Osteonecrosis of the femoral head (ONFH) is a common clinical disease with a high disability rate. Injury of bone microvascular endothelial cells (BMECs) caused by glucocorticoid administration is one of the important causes of ONFH, and there is currently a lack of effective clinical treatments. Extracellular vesicles derived from bone stem cells (BMSC-EVs) can prevent ONFH by promoting angiogenesis and can inhibit cell apoptosis by regulating autophagy via the PI3K/Akt/mTOR signaling pathway. The present study aimed to investigate the effect of extracellular vesicles derived from bone marrow stem cells (BMSC) on a glucocorticoid-induced injury of BMECs and possible mechanisms. We found that BMSC-EVs attenuated glucocorticoid-induced viability, angiogenesis capacity injury, and the apoptosis of BMECs. BMSC-EVs increased the LC3 level, but decreased p62 (an autophagy protein receptor) expression, suggesting that BMSC-Exos activated autophagy in glucocorticoid-treated BMECs. The protective effects of BMSC-EVs on the glucocorticoid-induced injury of BMECs was mimicked by a known stimulator of autophagy (rapamycin) and could be enhanced by co-treatment with an autophagy inhibitor (LY294002). BMSC-EVs also suppressed the PI3K/Akt/mTOR signaling pathway, which regulates cell autophagy, in glucocorticoid-treated BMECs. In conclusion, the results indicate that BMSC-EVs prevent the glucocorticoid-induced injury of BMECs by regulating autophagy via the PI3K/Akt/mTOR pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles from BMSCs Prevent Glucocorticoid-Induced BMECs Injury by Regulating Autophagy via the PI3K/Akt/mTOR Pathway

Shen

Yue

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…In a rat glaucoma model, neurosteroids induced the autophagy pathway to protect retinal neurons via GABRs/GABAA receptors [ 216 ]. However, another study reported that steroid therapy in the eye leads to the dysregulation of TMCs and glaucoma pathologies by inhibiting the autophagosome biogenesis pathway [ 217 ]. More studies are needed to conclude the effect of steroids on retinal neurons.…”

Section: Effects Of Autophagic Inducers and Inhibitors On Retinal Degenerative Diseasesmentioning

confidence: 99%

The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases

et al. 2022

View full text Add to dashboard Cite

Oxidative stress is mainly caused by intracellular reactive oxygen species (ROS) production, which is highly associated with normal physiological homeostasis and the pathogenesis of diseases, particularly ocular diseases. Autophagy is a self-clearance pathway that removes oxidized cellular components and regulates cellular ROS levels. ROS can modulate autophagy activity through transcriptional and posttranslational mechanisms. Autophagy further triggers transcription factor activation and degrades impaired organelles and proteins to eliminate excessive ROS in cells. Thus, autophagy may play an antioxidant role in protecting ocular cells from oxidative stress. Nevertheless, excessive autophagy may cause autophagic cell death. In this review, we summarize the mechanisms of interaction between ROS and autophagy and their roles in the pathogenesis of several ocular diseases, including glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and optic nerve atrophy, which are major causes of blindness. The autophagy modulators used to treat ocular diseases are further discussed. The findings of the studies reviewed here might shed light on the development and use of autophagy modulators for the future treatment of ocular diseases.

show abstract

“…More and more studies have shown that autophagy is closely related to the occurrence and development of SIONFH (21). It has been reported that excessive use of glucocorticoids can lead to autophagy disorders (22). Autophagy, as one of the forms of eukaryotic programmed cell death (type II programmed cell death), can help the body to remove useless and broken organelles, harmful macromolecules, and pathogenic microorganisms (23).…”

Section: Discussionmentioning

confidence: 99%

Plasma SQSTM1/p62 act as a biomarker for steroid-induced osteonecrosis of the femoral head

Hou,

Peng,

Xiao

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: Autophagy is closely associated with the onset and progression of steroid-induced osteonecrosis of the femoral head (SIONFH). SQSTM1/p62 is an important indicator of autophagic activity. The aim of this study was to investigate the role of SQSTM1/p62 in the development of SIONFH. Methods: From May 2021 through November 2021, 36 patients diagnosed with SIONFH and 36 healthy controls were recruited for this study. Evaluations included imaging and pathologic assessment of clinical bone tissue, location and level of SQSTM1/p62 expression, plasma SQSTM1/p62 levels, and receiver operating characteristic (ROC) curves. Results: We observed that the expression level of SQSTM1/p62 in bone samples decreased with the Association Research Circulation Osseous (ARCO) phase. Plasma SQSTM1/p62 levels were significantly higher in the SIONFH group compared to healthy controls. Plasma SQSTM1/p62 levels were higher in pre-crash patients than in post-crash patients, and lower plasma SQSTM1/p62 levels were associated with elevated ARCO stage. Conclusion: Plasma SQSTM1/p62 may represent a potential biomarker for different stages during SIONFH. Lower plasma SQSTM1/p62 levels indicate an advanced stage of SIONFH. This study provides new clues for early diagnosis of SIONFH.

show abstract

Dexamethasone Downregulates Autophagy through Accelerated Turn-Over of the Ulk-1 Complex in a Trabecular Meshwork Cells Strain: Insights on Steroid-Induced Glaucoma Pathogenesis

Cited by 19 publications

References 85 publications

Extracellular Vesicles from BMSCs Prevent Glucocorticoid-Induced BMECs Injury by Regulating Autophagy via the PI3K/Akt/mTOR Pathway

Extracellular Vesicles from BMSCs Prevent Glucocorticoid-Induced BMECs Injury by Regulating Autophagy via the PI3K/Akt/mTOR Pathway

The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases

Plasma SQSTM1/p62 act as a biomarker for steroid-induced osteonecrosis of the femoral head

Contact Info

Product

Resources

About