Protein Kinase C δ Deficiency Enhances Megakaryopoiesis and Recovery from Thrombocytopenia
Objective—We previously determined that protein kinase C δ (PKCδ) regulates platelet function. However, the function of PKCδ in megakaryopoiesis is unknown.
Approach and Results—Using PKCδ-/- and wild-type littermate mice, we found that deficiency of PKCδ caused an increase in white blood cells and platelet counts, as well as in bone marrow and splenic megakaryocytes (P<0.05). Additionally, the megakaryocyte number and DNA content were enhanced in PKCδ-/- mouse bone marrow after culturing with exogenous thrombopoietin compared with wild-type (P<0.05). Importantly, thrombopoietin-induced signaling was also altered with PKCδ deletion because both extracellular signal-regulated kinase and Akt308 phosphorylation were heightened in PKCδ-/- megakaryocytes compared with wild-type. Finally, PKCδ-/- mice recovered faster and had a heightened rebound thrombocytosis after thrombocytopenic challenge.
Conclusions—These data suggest that PKCδ is an important megakaryopoietic protein, which regulates signaling induced by thrombopoietin and represents a potential therapeutic target.
- Received April 23, 2014.
- Accepted October 13, 2014.
- © 2014 American Heart Association, Inc.