Dataset Information

N?-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway.

ABSTRACT: Background:Macrophage-derived foam cells play a central role in atherosclerosis, and their ultimate fate includes apoptosis, promotion of vascular inflammation, or migration to other tissues. N?-Carboxymethyl-lysine (CML), the key active component of advanced glycation end products, induced foam cell formation and apoptosis. Previous studies have shown that the Vav1/Rac1 pathway affects the macrophage cytoskeleton and cell migration, but its role in the pathogenesis of diabetic atherosclerosis is unknown. Methods and Results:In this study, we used anterior tibiofibular vascular samples from diabetic foot amputation patients and accident amputation patients, and histological and cytological tests were performed using a diabetic ApoE-/- mouse model and primary peritoneal macrophages, respectively. The results showed that the atherosclerotic plaques of diabetic foot amputation patients and diabetic ApoE-/- mice were larger than those of the control group. Inhibition of the Vav1/Rac1 pathway reduced vascular plaques and promoted the migration of macrophages to lymph nodes. Transwell and wound healing assays showed that the migratory ability of macrophage-derived foam cells was inhibited by CML. Cytoskeletal staining showed that advanced glycation end products inhibited the formation of lamellipodia in foam cells, and inhibition of the Vav1/Rac1 pathway restored the formation of lamellipodia. Conclusion:CML inhibits the migration of foam cells from blood vessels via the Vav1/Rac1 pathway, and this process affects the formation of lamellipodia.

SUBMITTER: Bao Z

PROVIDER: S-EPMC7064830 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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N<i>ε</i>-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway.

Bao Zhengyang Z Zhang Lili L Li Lihua L Yan Jinchuan J Pang Qiwen Q Sun Zhen Z Geng Yue Y Jing Lele L Shao Chen C Wang Zhongqun Z

Journal of immunology research 20200228

<h4>Background</h4>Macrophage-derived foam cells play a central role in atherosclerosis, and their ultimate fate includes apoptosis, promotion of vascular inflammation, or migration to other tissues. N<i>ε</i>-Carboxymethyl-lysine (CML), the key active component of advanced glycation end products, induced foam cell formation and apoptosis. Previous studies have shown that the Vav1/Rac1 pathway affects the macrophage cytoskeleton and cell migration, but its role in the pathogenesis of diabetic at ...[more]

PMID: 32190703

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Project description:In the developing cortex, excitatory neurons migrate along the radial fibers to their final destinations and build up synaptic connection with each other to form functional circuitry. The shaping of neuronal morphologies by actin cytoskeleton dynamics is crucial for neuronal migration. However, it is largely unknown how the distribution and assembly of the F-actin cytoskeleton are coordinated. In the present study, we found that an actin regulatory protein, coronin 2B, is indispensable for the transition from a multipolar to bipolar morphology during neuronal migration in ICR mice of either sex. Loss of coronin 2B led to heterotopic accumulation of migrating neurons in the intermediate zone along with reduced dendritic complexity and aberrant neuronal activity in the cortical plate. This was accompanied by increased seizure susceptibility, suggesting the malfunction of cortical development in coronin 2B-deficient brains. Coronin 2B knockdown disrupted the distribution of the F-actin cytoskeleton at the leading processes, while the migration defect in coronin 2B-deficient neurons was partially rescued by overexpression of Rac1 and its downstream actin-severing protein, cofilin. Our results collectively reveal the physiological function of coronin 2B during neuronal migration whereby it maintains the proper distribution of activated Rac1 and the F-actin cytoskeleton.SIGNIFICANCE STATEMENT Deficits in neuronal migration during cortical development result in various neurodevelopmental disorders (e.g., focal cortical dysplasia, periventricular heterotopia, epilepsy, etc.). Most signaling pathways that control neuronal migration process converge to regulate actin cytoskeleton dynamics. Therefore, it is important to understand how actin dynamics is coordinated in the critical processes of neuronal migration. Herein, we report that coronin 2B is a key protein that regulates neuronal migration through its ability to control the distribution of the actin cytoskeleton and its regulatory signaling protein Rac1 during the multipolar-bipolar transition in the intermediate zone, providing insights into the molecular machinery that drives the migration process of newborn neurons.

Dataset Information

N?-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway.

Publications

N<i>ε</i>-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway.

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