Mechanotransduction via a TRPV4-Rac1 signaling axis plays a role in multinucleated giant cell formation.

摘要: Multinucleated giant cells are formed by the fusion of macrophages and a characteristic feature in numerous pathophysiological conditions including foreign body response (FBR). Foreign (FBGCs) inflammatory destructive multinucleated may cause damage and/or rejection implants. However, while these features FBGCs well established, molecular mechanisms underlying their formation remain elusive. Improved understanding permit development novel implants that eliminate or reduce FBR. Our previous study showed transient receptor potential vanilloid 4 (TRPV4), mechanosensitive ion channel/receptor, is required for FBGC FBR to biomaterials. Here, we have determined (a) TRPV4 directly involved fusogenic cytokine (interleukin-4 plus granulocyte macrophage-colony stimulating factor)-induced activation Rac1, bone marrow-derived macrophages; (b) interacts with interaction further augmented presence cytokines; (c) TRPV4-dependent Rac1 essential augmentation intracellular stiffness regulation cytoskeletal remodeling; (d) TRPV4-Rac1 signaling axis critical cytokine-induced formation. Together, data suggest mechanism whereby functional between leads remodeling generation modulate