ABSTRACT
OBJECTIVE: To assess changes in plasma exosome levels and protein content in mice after long-term exercise. METHODS: We subjected 9-month-old adult C57BL/6J mice to daily treadmill running exercise for 4 weeks prior to the isolation of blood-derived exosomes. Exosomal proteins were identified using mass spectrometry. RESULTS: Extracellular bodies were successfully isolated from mouse blood. Protein levels were altered in blood-derived exosomes after chronic treadmill exercise. Levels of the secretagogue secretogranin 2 were markedly elevated in exercise-induced exosomes. CONCLUSION: Our data suggest that levels of secretogranin 2 were increased in mouse exosomes following chronic treadmill exercise. We conclude that exercise increases exocrine secretion of secretogranin 2.
Subject(s)
Exosomes , Physical Conditioning, Animal , Animals , Mass Spectrometry , Mice , Mice, Inbred C57BLABSTRACT
Myelin-laden macrophages (mye-MΦ), resulting primarily from internalization of myelin debris by infiltrating bone marrow-derived macrophages in spinal cord injury (SCI), trigger inflammatory responses that largely contribute to secondary injury. Adiponectin, which is secreted from adipose tissue, is an important hormone that modulates macrophage inflammation. In the present study, we examined the role of adiponectin on macrophage-mediated neuroinflammation after SCI. We found that in vitro activation of adiponectin receptors (AdipoRs) by their agonist AdipoRon suppressed myelin lipid accumulation in mye-MΦ through APPL1/PPARγ/LXRα/ABCA1-mediated lipid efflux, subsequently inhibiting inflammation and restoring normal function to mye-MΦ. In vivo data further confirmed that intravenous administration of AdipoRon after SCI dampened recruitment of macrophages and reduced myelin lipid accumulation. Accordingly, AdipoRon treatment ameliorated post-SCI tissue damage and astrogliosis, resulting in improved motor function. Although there was no significant pathological exacerbation in adiponectin-null mice subjected to SCI, our work reveals a functional link between adiponectin and hematogenous macrophages in the context of SCI, suggesting that activation of adiponectin signaling is a promising therapeutic approach to mitigate mye-MΦ-mediated neuroinflammation in neurological disorders involving demyelination.
Subject(s)
Adiponectin/metabolism , Macrophages/metabolism , Myelin Sheath/metabolism , Spinal Cord Injuries/physiopathology , Animals , Inflammation/metabolism , Inflammation/pathology , Inflammation/physiopathology , Lipids , Macrophage Activation/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Piperidines/pharmacology , Receptors, Adiponectin/agonists , Signal Transduction/drug effects , Signal Transduction/physiology , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/pathologyABSTRACT
Hemangioendothelioma (HE) is a type of angiomatous lesions that features endothelial cell proliferation. Understanding the mechanisms orchestrating HE angiogenesis can provide therapeutic insights. It has been shown that platelets can support normal and malignant endothelial cells during angiogenesis. Using the mouse endothelial-derived EOMA cell line as a model of HE, we explored the regulatory effect of platelets. We found that platelets stimulated EOMA proliferation but did not mitigate apoptosis. Furthermore, direct platelet-EOMA cell contact was required and the proliferation was mediated via integrin ß3/Akt signaling in EOMA cells. SiRNA knockdown of integrin ß3 and inhibition of Akt activity significantly abolished platelet-induced EOMA cell proliferation in vitro and tumor development in vivo. These results provide a new mechanism by which platelets support HE progression and suggest integrin ß3 as a potential target to treat HE.
