Activating Adiponectin Signaling with Exogenous AdipoRon Reduces Myelin Lipid Accumulation and Suppresses Macrophage Recruitment after Spinal Cord Injury.

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.

Integrin ß3/Akt signaling contributes to platelet-induced hemangioendothelioma growth.

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.