Pioglitazone alleviates inflammation in diabetic mice fed a high‐fat diet via inhibiting advanced glycation end‐product‐induced classical macrophage activation

Jin, Xian; Liu, Liang; Zhou, Zhong’e; Ge, Junhua; Yao, Tongqing; Shen, Chengxing

doi:10.1111/febs.13735

Cited by 20 publications

(16 citation statements)

References 35 publications

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“…Previous study has demonstrated inflammation in diabetes, which features NF-κB activation induced by AGEs18. Thus, we examined the effects of Myr on NF-κB signaling and the inflammatory cytokine, TNF-α.…”

Section: Resultsmentioning

confidence: 97%

Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy

Zhang

Shen

Chen

et al. 2017

Sci Rep

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Diabetic cardiomyopathy (DCM) has been increasingly considered as a main cause of heart failure and death in diabetic patients. At present, no effective treatment exists to prevent its development. In the present study, we describe the potential protective effects and mechanisms of myricitrin (Myr) on the cardiac function of streptozotosin-induced diabetic mice and on advanced glycation end products (AGEs)-induced H9c2 cardiomyocytes. In vitro experiments revealed that pretreatment with Myr significantly decreased AGEs-induced inflammatory cytokine expression, limited an increase in ROS levels, and reduced cell apoptosis, fibrosis, and hypertrophy in H9c2 cells. These effects are correlated with Nrf2 activation and NF-κB inhibition. In vivo investigation demonstrated that oral administration of Myr at 300 mg/kg/day for 8 weeks remarkably decreased the expression of enzymes associated with cardiomyopathy, as well as the expression of inflammatory cytokines and apoptotic proteins. Finally, Myr improved diastolic dysfunction and attenuated histological abnormalities. Mechanistically, Myr attenuated diabetes-induced Nrf2 inhibition via the regulation of Akt and ERK phosphorylation in the diabetic heart. Collectively, these results strongly indicate that Myr exerts cardioprotective effects against DCM through the blockage of inflammation, oxidative stress, and apoptosis. This suggests that Myr might be a potential therapeutic agent for the treatment of DCM.

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Section: Resultsmentioning

confidence: 97%

Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy

Zhang

Shen

Chen

et al. 2017

Sci Rep

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“…Monocytes and macrophages play vital roles in the formation and progression of atherosclerosis. Increased proportions of circulating monocytes, especially the inflammatory type, might be associated with accelerated atherosclerosis in diabetes which have been documented in diabetic Akita mice [ 1 ] and in STZ-induced diabetic mice [ 2 , 3 ]. Nagareddy et al's work [ 2 ] demonstrated that high glucose drives bone marrow myelopoiesis and promotes diabetes-associated atherogenesis.…”

Section: Introductionmentioning

confidence: 99%

Advanced Glycation End Products Enhance Murine Monocyte Proliferation in Bone Marrow and Prime Them into an Inflammatory Phenotype through MAPK Signaling

Jin

Liu

Zhang

et al. 2018

Journal of Diabetes Research

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Objective Increased monocytes, particularly the inflammatory subset, are associated with accelerated atherosclerosis in diabetes through thus far incompletely defined mechanisms. The present study tested the hypothesis that advanced glycation end products (AGEs) promote bone marrow monocytes to proliferate and drive them into an inflammatory phenotype. Methods and Results In vivo, AGEs (25 mg/kg i.p. for 7 days) increased proportions of CD115+ monocytes and the inflammatory subset, the CD115+Ly6Chigh cells, in murine bone marrow (flow cytometry analysis (FCM)), and enhanced gene expression of proinflammatory cytokines (IL-1β and TNF-α) but only slightly upregulated mRNA expression of anti-inflammatory cytokine (IL-10) (real-time PCR) in monocytes. In vitro, when the monocytes were treated with different dosages of AGEs (50, 150, and 300 μg/mL), we found that proliferation (CCK8) but not apoptosis (FCM) of the monocytes was induced; the mRNA expressions of proinflammatory cytokines (IL-1β and TNF-α) and GM-CSF were upregulated in a dose-dependent manner while mRNA levels of IL-10 and M-CSF were changed much less in monocytes (real-time PCR). Furthermore, AGEs (300 μg/mL) significantly enhanced the expression of Ki67 in monocytes (immunofluorescence staining (IF)), and this dose of AGEs markedly increased secretion of GM-CSF but not that of M-CSF (ELISA). For a pathway study, the monocytes were stimulated by 300 μg/mL AGEs for different periods of time (0, 15, 30, and 120 min) and the activation of the MAPK pathway was tested (FCM); the results showed the p38 and ERK pathways were activated but not JNK signaling. Pretreatment with an inhibitor of p38 (SB203580) or ERK (U0126) attenuated AGE-induced gene expression of proinflammatory cytokines and GM-CSF (real-time PCR), as well as reversing AGE-induced Ki67 expression (IF). Conclusions AGEs promote bone marrow monocytes to proliferate and drive them into an inflammatory phenotype through p38 and ERK activation.

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“…Previous studies have demonstrated that excessive inflammatory M1 monocytes/macrophages emerge in peripheral blood of both prediabetic and diabetic patients [ 4 , 5 ]. Furthermore, our previous study also found that M1 monocytes/macrophages, the inflammatory subset, increased in circulation and atherosclerotic plaque in STZ-induced diabetic mice and were related to enhanced inflammation and accelerated atherosclerosis [ 6 ]. Thus, the increased inflammatory macrophages in diabetes contribute to persistent low grade inflammation and accelerated atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Metformin Inhibits Advanced Glycation End Products-Induced Inflammatory Response in Murine Macrophages Partly through AMPK Activation and RAGE/NFκB Pathway Suppression

Zhou

Tang

Jin

et al. 2016

Journal of Diabetes Research

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Advanced glycation end products (AGEs) are major inflammatory mediators in diabetes, affecting atherosclerosis progression via macrophages. Metformin slows diabetic atherosclerosis progression through mechanisms that remain to be fully elucidated. The present study of murine bone marrow derived macrophages showed that (1) AGEs enhanced proinflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) mRNA expression, RAGE expression, and NFκB activation; (2) metformin pretreatment inhibited AGEs effects and AGEs-induced cluster designation 86 (CD86) (M1 marker) expression, while promoting CD206 (M2 marker) surface expression and anti-inflammatory cytokine (IL-10) mRNA expression; and (3) the AMPK inhibitor, Compound C, attenuated metformin effects. In conclusion, metformin inhibits AGEs-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFκB pathway suppression.

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Pioglitazone alleviates inflammation in diabetic mice fed a high‐fat diet via inhibiting advanced glycation end‐product‐induced classical macrophage activation

Cited by 20 publications

References 35 publications

Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy

Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy

Advanced Glycation End Products Enhance Murine Monocyte Proliferation in Bone Marrow and Prime Them into an Inflammatory Phenotype through MAPK Signaling

Metformin Inhibits Advanced Glycation End Products-Induced Inflammatory Response in Murine Macrophages Partly through AMPK Activation and RAGE/NFκB Pathway Suppression

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