The protective effect of EGF‐activated ROS in human corneal epithelial cells by inducing mitochondrial autophagy via activation TRPM2

Huo, Yanyan; Chen, Wei; Zheng, Xiaoxiao; Zhao, Jinchuan; Zhang, Qi; Hou, Yuerou; Cai, Ying; Lu, Xuemei; Jin, Xiuming

doi:10.1002/jcp.29597

Cited by 16 publications

(8 citation statements)

References 44 publications

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“…ROS are the byproducts of oxygen and are produced due to cellular metabolism, and regulate the redox balance, proliferation, cytotoxicity, and metabolic adaptation in a concentration-dependent manner [ 47 , 53 – 56 ]. In the CE, ROS production is triggered by damage outside the eye (including chemical- or UV light-induced damage, and mechanical damage), as well as by inflammatory factors in the aqueous humour or tears [ 57 – 59 ].…”

Section: Interactions Between Ros and Akt In Cecsmentioning

confidence: 99%

The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates

Chen

Zhang

et al. 2022

Cell Death Dis

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Phosphatidylinositol 3 kinase (PI3K)/AKT (also called protein kinase B, PKB) signalling regulates various cellular processes, such as apoptosis, cell proliferation, the cell cycle, protein synthesis, glucose metabolism, and telomere activity. Corneal epithelial cells (CECs) are the outermost cells of the cornea; they maintain good optical performance and act as a physical and immune barrier. Various growth factors, including epidermal growth factor receptor (EGFR) ligands, insulin-like growth factor 1 (IGF1), neurokinin 1 (NK-1), and insulin activate the PI3K/AKT signalling pathway by binding their receptors and promote antiapoptotic, anti-inflammatory, proliferative, and migratory functions and wound healing in the corneal epithelium (CE). Reactive oxygen species (ROS) regulate apoptosis and inflammation in CECs in a concentration-dependent manner. Extreme environments induce excess ROS accumulation, inhibit PI3K/AKT, and cause apoptosis and inflammation in CECs. However, at low or moderate levels, ROS activate PI3K/AKT signalling, inhibiting apoptosis and stimulating proliferation of healthy CECs. Diabetes-associated hyperglycaemia directly inhibit PI3K/AKT signalling by increasing ROS and endoplasmic reticulum (ER) stress levels or suppressing the expression of growth factors receptors and cause diabetic keratopathy (DK) in CECs. Similarly, hyperosmolarity and ROS accumulation suppress PI3K/AKT signalling in dry eye disease (DED). However, significant overactivation of the PI3K/AKT signalling pathway, which mediates inflammation in CECs, is observed in both infectious and noninfectious keratitis. Overall, upon activation by growth factors and NK-1, PI3K/AKT signalling promotes the proliferation, migration, and anti-apoptosis of CECs, and these processes can be regulated by ROS in a concentration-dependent manner. Moreover, PI3K/AKT signalling pathway is inhibited in CECs from individuals with DK and DED, but is overactivated by keratitis.

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Section: Interactions Between Ros and Akt In Cecsmentioning

confidence: 99%

The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates

Chen

Zhang

et al. 2022

Cell Death Dis

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“…Besides, Beclin-1 promotes the initiation of autophagy by mediating the formation of autophagosomes. However, p62 aggregates outside the lysosomes and is involved in selective autophagy [23], in which the first steps of autophagy are impaired [24]. This knowledge was used to speculate on the trend of autophagy in cells, by detecting the changes in p62, Beclin-1, and LC3B protein expression.…”

Section: Discussionmentioning

confidence: 99%

Elucidation of SIRT-1/PGC-1α-associated mitochondrial dysfunction and autophagy in nonalcoholic fatty liver disease

et al. 2021

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Background Nonalcoholic fatty liver disease (NAFLD) can lead to chronic liver diseases associated with mitochondrial damages. However, the exact mechanisms involved in the etiology of the disease are not clear. Methods To gain new insights, the changes affecting sirtuin 1 (SIRT-1) during liver fat accumulation was investigated in a NAFLD mouse model. In addition, the in vitro research investigated the regulation operated by SIRT-1 on mitochondrial structures, biogenesis, functions, and autophagy. Results In mice NAFLD, high-fat-diet (HFD) increased body weight gain, upregulated serum total cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, blood glucose, insulin levels, and liver malondialdehyde, and decreased liver superoxide dismutase activity. In liver, the levels of SIRT-1 and peroxisome proliferator-activated receptor-gamma coactivator -1α (PGC-1α) decreased. The expression of peroxisome proliferator-activated receptor-α and Beclin-1 proteins was also reduced, while p62/SQSTM1 expression increased. These results demonstrated SIRT-1 impairment in mouse NAFLD. In a well-established NAFLD cell model, exposure of the HepG2 hepatocyte cell line to oleic acid (OA) for 48 h caused viability reduction, apoptosis, lipid accumulation, and reactive oxygen species production. Disturbance of SIRT-1 expression affected mitochondria. Pre-treatment with Tenovin-6, a SIRT-1 inhibitor, aggravated the effect of OA on hepG2, while this effect was reversed by CAY10602, a SIRT-1 activator. Further investigation demonstrated that SIRT-1 activity was involved in mitochondrial biogenesis through PGC-1α and participated to the balance of autophagy regulatory proteins. Conclusion In conclusion, in high-fat conditions, SIRT-1 regulates multiple cellular properties by influencing on mitochondrial physiology and lipid autophagy via the PGC-1α pathway. The SIRT-1/PGC-1α pathway could be targeted to develop new NAFLD therapeutic strategies.

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“…It suppressed the proliferation, migration, fibrosis, and invasion of rabbit corneal stromal cells, facilitated the autophagy and the differentiation of corneal cells [ 65 ]. In scratch injured HCECs, treatment with epidermal growth factor (EGF) could activate the transient receptor potential cation channel subfamily M member 2 pathway by upregulating reactive oxygen species (ROS)-induced calcium influx to activate mitochondrial autophagy and inhibit apoptosis, and finally promote the repairment of HCECs [ 66 ]. H 2 O 2 -induced corneal oxidative injury inhibited the autophagy process, and rapamycin, a common autophagy activator, could reverse and ameliorate the condition.…”

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

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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.

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The protective effect of EGF‐activated ROS in human corneal epithelial cells by inducing mitochondrial autophagy via activation TRPM2

Cited by 16 publications

References 44 publications

The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates

The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates

Elucidation of SIRT-1/PGC-1α-associated mitochondrial dysfunction and autophagy in nonalcoholic fatty liver disease

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

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