PG545 alleviates diabetic retinopathy by promoting retinal Müller cell autophagy to inhibit the inflammatory response

Wang, Ying; Liu, Xiaojuan; Zhu, Linling; Li, Wendie; Li, Zhizhe; Lu, Xiting; Liu, Jie; Hua, Wenjuan; Zhou, Yamei; Gu, Yong-Hui; Zhu, Manhui

doi:10.1016/j.bbrc.2020.07.134

Cited by 15 publications

(8 citation statements)

References 32 publications

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“…At variance with the previous reported results, in the retina of STZ-induced diabetic mice a decrease of Beclin-1, Atg7, p62 and LC3-II expression was reported as compared to control group; treatment with the heparanase inhibitor PG545 promoted autophagy and inhibited the secretion of pro-inflammatory cytokines alleviating diabetic retinopathy (Wang et al, 2020).Similarly, in STZ-induced diabetic C57BL/6J mice, as well as in Bio-Breeding Zucker diabetic (BBZDR/Wor) rats that spontaneously develop a T2D, Qi and colleagues reported a dramatic reduction of Atg7, Atg9, LC3 and Beclin-1 in diabetic retina as compared to controls (Qi et al, 2020).…”

Section: The Role Of Autophagy In Animal Models Of Diabetic Retinopathycontrasting

confidence: 97%

Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy

et al. 2021

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Autophagy is the major catabolic pathway involved in removing and recycling damaged macromolecules and organelles and several evidences suggest that dysfunctions of this pathway contribute to the onset and progression of central and peripheral neurodegenerative diseases. Diabetic retinopathy (DR) is a serious complication of diabetes mellitus representing the main preventable cause of acquired blindness worldwide. DR has traditionally been considered as a microvascular disease, however this concept has evolved and neurodegeneration and neuroinflammation have emerged as important determinants in the pathogenesis and evolution of the retinal pathology. Here we review the role of autophagy in experimental models of DR and explore the potential of this pathway as a target for alternative therapeutic approaches.

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Section: The Role Of Autophagy In Animal Models Of Diabetic Retinopathycontrasting

confidence: 97%

Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy

et al. 2021

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“…DR is a microvascular complication of diabetes, which is characterized by the loss of retinal capillary pericytes and increased vascular permeability [ 5 ]. Studies have confirmed that inflammation promotes the development of DR [ 6 – 8 ]. Chronic inflammation can cause dysfunction of the retinal endothelial cells, reduce pericytes, and increase vascular permeability, which contribute to the progression of DR [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell Exosomal miR-146a Mediates the Regulation of the TLR4/MyD88/NF-κB Signaling Pathway in Inflammation due to Diabetic Retinopathy

Zhang

Zhao

et al. 2022

Computational and Mathematical Methods in Medicine

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Diabetic retinopathy (DR) is the main cause of vision loss in diabetic patients, which cannot be completely resolved by typical blood sugar control. Inflammation influences the development of DR, so reducing the inflammatory response in DR patients is crucial to the prevention of DR. Therefore, we explored the regulatory effect of bone marrow mesenchymal stem cell (BMSC) exosomes on inflammation in DR mice. In order to analyze the mechanism of action, we used BMSC exosomal miR-146a to treat microglias in DR mice to observe cellular changes and expression of inflammatory factors. It was found that BMSC exosomal miR-146a reduced the levels of proliferating cell antigen and B-cell lymphoma-2 in microglias of DR mice and increased Bcl-2-related X with cysteine aspartic protease-3. By analyzing the expression of inflammatory factors, we found that BMSC exosomal miR-146a reduced the levels of TNF-α, IL-1β, and IL-6, which suggested that miR-146a can alleviate inflammation in DR mice. Further exploration found that miR-146a reduced the activity of TLR4 and increased the activity of MyD88 and NF-κB. Furthermore, the overexpression of TLR4 reversed the effects of miR-146a on the proliferation, apoptosis, and inflammation of microglias. Our study demonstrated that BMSC exosomal miR-146a can regulate the inflammatory response of DR by mediating the TLR4/MyD88/NF-κB pathway, providing an experimental basis for the prevention and treatment of DR.

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“…Most glial cells are Müller cells that exist in all retinal layers; they can provide energy for neurons and are also the main source of VEGF. Wang Y. et al, 2020 showed that the expression of Beclin-1, Atg7, and LC3-IIof Müller cells in the retina of STZ-induced diabetic mice were lower than those in the control group. Autophagy could be promoted by inhibiting the mTOR pathway, which could inhibit the secretion of inflammatory factors and retard the progression of DR. Other studies show that the expression of Beclin-1 and LC3-II were upregulated in Müller cells under HG, which indicated the existence of autophagosomes.…”

Section: The Molecular Mechanism Of Autophagy and Diabetic Microvascu...mentioning

confidence: 91%

Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy

Liu,

Zhao,

et al. 2024

Front. Pharmacol.

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As the quality of life improves, the incidence of diabetes mellitus and its microvascular complications (DMC) continues to increase, posing a threat to people’s health and wellbeing. Given the limitations of existing treatment, there is an urgent need for novel approaches to prevent and treat DMC. Autophagy, a pivotal mechanism governing metabolic regulation in organisms, facilitates the removal of dysfunctional proteins and organelles, thereby sustaining cellular homeostasis and energy generation. Anomalous states in pancreatic β-cells, podocytes, Müller cells, cardiomyocytes, and Schwann cells in DMC are closely linked to autophagic dysregulation. Natural products have the property of being multi-targeted and can affect autophagy and hence DMC progression in terms of nutrient perception, oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis. This review consolidates recent advancements in understanding DMC pathogenesis via autophagy and proposes novel perspectives on treating DMC by either stimulating or inhibiting autophagy using natural products.

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PG545 alleviates diabetic retinopathy by promoting retinal Müller cell autophagy to inhibit the inflammatory response

Cited by 15 publications

References 32 publications

Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy

Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy

Mesenchymal Stem Cell Exosomal miR-146a Mediates the Regulation of the TLR4/MyD88/NF-κB Signaling Pathway in Inflammation due to Diabetic Retinopathy

Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy

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