Sirt1 attenuates diabetic keratopathy by regulating the endoplasmic reticulum stress pathway

Wei, Shuang; Fan, Jianwu; Zhang, Xin; Jiang, Yaping; Zeng, Siliang; Pan, Xin; Sheng, Mao; Chen, Yihui

doi:10.1016/j.lfs.2020.118789

Cited by 8 publications

(4 citation statements)

References 37 publications

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“…Hyperglycaemic conditions induce mitochondrial fragmentation, which leads to ROS overproduction that inactivates PI3K/AKT [ 74 ]. Silent information regulator 1 (SIRT1) is a substrate of PI3K/AKT signalling that decreases ROS production, apoptosis, and endoplasmic reticulum (ER) stress in CECs in vitro [ 75 ]. Hyperglycaemia reduces SIRT1 expression, increases P53 acetylation, and inhibits the IGF1/PI3K/AKT cascade in CECs, which may cause delayed healing of the CE in vivo and in vitro [ 76 , 77 ].…”

Section: Diseases Their Therapies 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: Diseases Their Therapies 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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“…The performance of KEGG and GO help gain insight of potential function enriched in, of these pathways we revealed that the most important pathway was glycosphingolipid biosynthesis, mucin type O-Glycan biosynthesis and bacterial invasion of epithelial cells. Many studies also have indicated the role of activation of RAS [39,40] or AMPK [41] in diabetic keratopathy. There were also several studies about the cGMP-PKG signaling pathway [42] and Insulin signaling pathway [29] Moreover, previous studies have revealed exosomes can transfer miRNAs to proximal or distal cells [43,44].…”

Section: Discussionmentioning

confidence: 99%

Effect of Tear Derived Exosomes on Corneal Epithelial Cells During Diabetic Keraropathy

Wang

Liu

et al. 2022

Preprint

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Background: As reliable intercellular transporters, exosomes for the diagnosis and function of various disease are fully explored. Also, exosomes extracted from tear film have been used as indictors for various eye disease, even systemic disease due to the easy and non-invasive collection nature with microRNAs variation. However, there still no reports focus the change and function of on exosomes and exosomal microRNAs during diabetes ocular dysfunction.Methods: Paired diabetes and health tear film-derived exosomes were collected by test strips and identified according standard regimens. Different expression microRNAs were profiled by microarray. The function of exosomes to cornea epithelium was detected by cornea wound model in vivo and cell viability and migration assay in vitro. Bioinformatics analysis, including GO and KEGG were conducted to explore the potential biological signaling pathway.Results: We confirmed diabetic tear film derived exosomes contribute to delay cornea wound healing and aggravate diabetic dry eye-like syndrome. Total 12 differential expression microRNAs were confirmed compared with paired controls, may participate in glycosphingolipid biosynthesis; mucin type O-Glycan biosynthesis; Ras signaling pathway; AMPK signaling pathway; bacterial invasion of epithelial cells; ErbB signaling pathway; cGMP-PKG signaling pathwayConclusion: This study provides evidence that diabetic tear film derived exosomes can affect the ocular surface health during diabetes, while healthy exosomes have no similar effects. Thus, the different expression of microRNAs existed in the exosomes from diabetes and healthy volunteer may be the reason of different function.

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“…Furthermore, in mice, oxidative stress results in pathogenic modification of the acinar cells in the lacrimal gland. Another research revealed that DED was clearly associated with silent mating type information regulation 2 homolog 1 (SIRT1) overexpression [ 60 ]. Sirt1 expression has an impact on the endoplasmic reticulum stress pathway’s regulation, slows the degeneration of corneal epithelial cells, and modulates the pathological course of diabetic keratopathy [ 60 ].…”

Section: Corneal Alterations and Pathogenesis In Diabetes Mellitusmentioning

confidence: 99%

Immune-Mediated Ocular Surface Disease in Diabetes Mellitus—Clinical Perspectives and Treatment: A Narrative Review

Ghenciu,

Hațegan,

Bolintineanu

et al. 2024

Biomedicines

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Diabetes mellitus (DM) is a chronic metabolic disorder marked by hyperglycemia due to defects in insulin secretion, action, or both, with a global prevalence that has tripled in recent decades. This condition poses significant public health challenges, affecting individuals, healthcare systems, and economies worldwide. Among its numerous complications, ocular surface disease (OSD) is a significant concern, yet understanding its pathophysiology, diagnosis, and management remains challenging. This review aims to explore the epidemiology, pathophysiology, clinical manifestations, diagnostic approaches, and management strategies of diabetes-related OSD. The ocular surface, including the cornea, conjunctiva, and associated structures, is vital for maintaining eye health, with the lacrimal functional unit (LFU) playing a crucial role in tear film regulation. In DM, changes in glycosaminoglycan metabolism, collagen synthesis, oxygen consumption, and LFU dysfunction contribute to ocular complications. Persistent hyperglycemia leads to the expression of cytokines, chemokines, and cell adhesion molecules, resulting in neuropathy, tear film abnormalities, and epithelial lesions. Recent advances in molecular research and therapeutic modalities, such as gene and stem cell therapies, show promise for managing diabetic ocular complications. Future research should focus on pathogenetically oriented therapies for diabetic neuropathy and keratopathy, transitioning from animal models to clinical trials to improve patient outcomes.

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Sirt1 attenuates diabetic keratopathy by regulating the endoplasmic reticulum stress pathway

Cited by 8 publications

References 37 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

Effect of Tear Derived Exosomes on Corneal Epithelial Cells During Diabetic Keraropathy

Immune-Mediated Ocular Surface Disease in Diabetes Mellitus—Clinical Perspectives and Treatment: A Narrative Review

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