LXRβ is involved in the control of platelet production from megakaryocytes

Liver X receptor β (LXRβ), a nuclear receptor involved in important cellular processes such as cholesterol, glucose and fatty acid metabolism, was suggested to be involved in platelet aggregation but its detailed roles are not clear. In the present study, we evaluated the contribution of LXRβ to platelet functions and production. In the systemic collagen-epinephrine thrombosis mouse model, LXRβ-deficient mice showed increased area of blood clots compared with control wide-type littermates. The aggregation of LXRβ-deficient platelets in response to ADP was stronger than that of control mice platelets. More importantly, the number of platelets in blood of LXRβ-deficient mice was significantly higher than that of wild-type mice, especially for female mice. Knockdown of LXRβ expression in human megakaryoblastic Dami cells also enhanced cell polyploidization, formation of proplatelets and production of platelet-like particles. Increase in expression levels of proteins related to oxidative phosphorylation such as NADH:ubiquinone oxidoreductase core subunit V1 (Ndufv1) was observed in LXRβ-knockdown Dami cells. The levels of Ndufv1 in LXRβ-deficient mice platelets were also higher than that of wild-type mice. Taken together, our findings suggested LXRβ might participate in control of platelet production from megakaryocytes by regulating mitochondrial metabolism.