AGEs Induced Autophagy Impairs Cutaneous Wound Healing via Stimulating Macrophage Polarization to M1 in Diabetes

Guo, Yuanyuan; Cai, Lin; Xu, Peng; Wu, Shan; Fu, Xiaokang; Xia, Weidong; Yao, Min

doi:10.1038/srep36416

Cited by 105 publications

(89 citation statements)

References 41 publications

(49 reference statements)

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“…To observe the effects of AFB 1 on the polarization of SIV-infected PAMs, PAMs were seeded on coverslips and infected with SIV for 24 h. Subsequently, groups of cells were further exposed to polarizing cytokines and AFB 1 for an additional 24 h, as follows: Group 1 (M1 control): LPS (100 ng/ml) plus IFN-γ (25 ng/ ml); Group 2 (M2 control): IL-4 (25 ng/ml) [30][31][32]; Group 3: AFB 1 (0 µg/ml); Group 4: AFB 1 (0.02 µg/ml); and Group 5: AFB 1 (0.04 µg/ml). At the end of the incubation period, PAMs were washed three times with PBS and were then fixed in 2.5% glutaraldehyde for 4 h at 4°C.…”

Section: Observation Of Pam Polarization By Scanning Electron Microscopymentioning

confidence: 99%

Low-Level Aflatoxin B1 Promotes Influenza Infection and Modulates a Switch in Macrophage Polarization from M1 to M2

Sun

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Swine influenza virus (SIV) is a major pathogen of both animals and humans. Afatoxin B1 (AFB₁) is one of the most common mycotoxins in feed and food. However, the central contribution of AFB₁ to SIV infection remains unclear. Methods: Here, TCID₅₀ assays, fluorescence-based quantitative real-time PCR, western blotting, immunofluorescence staining, histopathological examination, flow cytometry and scanning electron microscopy were performed to investigate the involvement and underlying mechanism of AFB₁ in SIV infection in vivo and in vitro using mouse models and porcine alveolar macrophage (PAM) models, respectively. Results: The in vivo study showed that low levels of AFB₁ promoted SIV infection and increased its severity, as demonstrated by the increased mRNA expression of viral matrix protein (M); by the increased protein expression of nucleoprotein (NP), matrix protein 1 and ion channel protein; and by animal weight loss, lung index and lung histologic damage. In addition, the increased occurrence of SIV infection accompanied by increases in the level of IL-10 in sera and lungs, in the spleen index and in the number of CD206-positive mouse alveolar macrophages but decreases in the level of TNF-α in sera and lungs, in the thymus index and in the number of CD80-positive mouse alveolar macrophages was observed in SIV-infected mice after low-level AFB₁ exposure. The in vitro study showed that low concentrations of AFB₁ promoted SIV infection, as demonstrated by the increases in viral titers and viral M mRNA and NP expression levels in SIV-infected PAMs as well as by the number of cells positive for NP protein expression. Furthermore, AFB₁ promoted the polarization of SIV-infected PAMs to the M1 phenotype at 8 hpi and to the M2 phenotype at 24 hpi, as measured by the increases in IL-10 expression and in the number of CD206-positive PAMs as well as by the morphological changes observed by scanning electron microscopy. The administration of the immune stimulant lipopolysaccharide (LPS) reversed the switch in PAM polarization from M2 to M1 and thereby counteracted the promotion of influenza virus infection induced by AFB₁. Conclusion: Our results are the first to confirm that low-level exposure to AFB₁ promotes SIV infection and modulates a switch in macrophage polarization from M1 to M2. The work reported here provides important data that point to a role for AFB₁ in SIV infection, and it opens a new field of study.

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Section: Observation Of Pam Polarization By Scanning Electron Microscopymentioning

confidence: 99%

Low-Level Aflatoxin B1 Promotes Influenza Infection and Modulates a Switch in Macrophage Polarization from M1 to M2

Sun

Liu

et al. 2018

Cell Physiol Biochem

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“…IRF8 has been characterized, in previous research, to be a central element and functions downstream of the IFN-γ signaling pathway that involves IFN-γ's binding to the receptor STAT1 and is recognized to regulate the activation of the proin ammatory M1 phenotype macrophages [22]. Consistently, IRF8 activation was also proved to induce M1 polarization of macrophages after advanced glycation endproducts treatment previously [23]. Moreover, IRF8 could be controlled by the Notch-RBP-J signaling pathway to participate in the regulation of TLR-induced in ammatory polarization of macrophages, namely the M1 macrophages polarization [24].…”

Section: Discussionmentioning

confidence: 78%

Interferon regulatory factor 8 induces alveolar macrophage hypoxia/reoxygenation injury via the PINK1/Parkin mitophagy pathway

Zhang¹,

Hu²,

He³

et al. 2020

Preprint

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Background: Lung ischemia-reperfusion injury (LIRI) is a complex process and macrophages play a central role in it. Interferon regulatory factor 8 (IRF8) is a transcription factor in the innate immune system, which, together with autophagy, are important components of the mechanisms of LIRI. We aimed to explore the regulatory role of IRF8 in hypoxia/reoxygenation (HR) injury and PINK1-mediated mitophagy.Methods: Cultured NR8383 macrophages were subjected to HR as an in vitro model of LIRI. Cell viability, cell damage and inflammation during HR were evaluated by Cell Counting Kit-8 assay, lactate dehydrogenase assessment and enzyme linked immunosorbent assay, respectively. Meanwhile, PINK1/Parkin-mediated mitochondrial autophagy was detected by quantitative real-time PCR, western blot, transmission electron microscopy and double immunofluorescence labeling method. The effects of IRF8 and PINK1 on cell injury, inflammatory response and autophagy during HR were assessed using IRF8 short-hairpin RNA plasmids and PINK1 overexpression plasmids , respectively. Results: IRF8 inhibition was able to alleviate cell injury, inflammatory response and autophagy while PINK1 overexpression could exacerbate them. Moreover, IRF8 downregulation could reduce the expression of PINK1 in HR injury and attenuate the effects of it. Conclusion: IRF8 was able to induce HR injury via the PINK1/Parkin mitophagy pathway. Inhibition of IRF8 and PINK1/Parkin-mediated mitophagy might be a potential target for the treatment of LIRI.

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“…Autophagy also plays a role in oxidative injury . AGE‐induced autophagy has been linked to impaired cutaneous wound healing through stimulation of the M1 polarized macrophage . M1 macrophages promote inflammation, and prolonged inflammation has been noted in delayed wound healing.…”

Section: Wound Healingmentioning

confidence: 99%

“…M1 macrophages promote inflammation, and prolonged inflammation has been noted in delayed wound healing. Additionally, Guo and colleagues reported that in the presence of AGEs, the autophagy regulator IRF8 is upregulated, suggesting that in diabetes autophagy is excessive and linked to delayed wound healing.…”

Section: Wound Healingmentioning

confidence: 99%

The link between advanced glycation end products and apoptosis in delayed wound healing

Shaikh-Kader

Houreld

Rajendran

et al. 2019

Cell Biochemistry & Function

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Advanced glycation end products (AGEs) are naturally occurring molecules that start to accumulate from embryonic developmental stages and form as part of normal ageing. When reducing sugars interact with and modify proteins or lipids, AGE production occurs. AGE formation accelerates in chronic hyperglycemic conditions, and high AGE levels have been associated with the pathogenesis of various diseases. In addition, enhanced levels of AGEs have been linked to delayed wound healing as seen in patients with diabetes mellitus. Research has provided numerous ways in which a high AGE concentration results in impaired wound healing, including oxidative stress, structural and functional changes to proteins important in wound repair, an enhanced inflammatory response by activation of transcription factors, and possible exaggerated apoptosis of cells necessary to the wound repair process. Apoptosis is a naturally occurring cell death process that is significant for normal tissue functioning and plays an important role in wound repair by preventing a prolonged inflammatory response and excessive scar formation. Abnormal apoptosis affects wound healing, resulting in slow healing wounds. This review will summarize the role of AGEs in wound healing, focusing on the mechanisms by which AGEs lead to apoptosis in various cell types. The review provides the way forward for medical research and molecular studies as it focuses on the mechanisms by which AGEs induce apoptosis in various cell types, including fibroblasts, osteoblasts, neuronal cells, and endothelial cells. Reviewing the mechanisms of AGE‐linked apoptosis is important in understanding the impact of high AGE levels in delayed wound healing in diabetic patients due to abnormal apoptosis of cells necessary to the wound healing process.

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AGEs Induced Autophagy Impairs Cutaneous Wound Healing via Stimulating Macrophage Polarization to M1 in Diabetes

Cited by 105 publications

References 41 publications

Low-Level Aflatoxin B1 Promotes Influenza Infection and Modulates a Switch in Macrophage Polarization from M1 to M2

Low-Level Aflatoxin B1 Promotes Influenza Infection and Modulates a Switch in Macrophage Polarization from M1 to M2

Interferon regulatory factor 8 induces alveolar macrophage hypoxia/reoxygenation injury via the PINK1/Parkin mitophagy pathway

The link between advanced glycation end products and apoptosis in delayed wound healing

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