| First Author | Kostyak JC | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 8 | Pages | e0182867 |
| PubMed ID | 28783756 | Mgi Jnum | J:246831 |
| Mgi Id | MGI:5916548 | Doi | 10.1371/journal.pone.0182867 |
| Citation | Kostyak JC, et al. (2017) PKC-epsilon deficiency alters progenitor cell populations in favor of megakaryopoiesis. PLoS One 12(8):e0182867 |
| abstractText | BACKGROUND: It has long been postulated that Protein Kinase C (PKC) is an important regulator of megakaryopoiesis. Recent contributions to the literature have outlined the functions of several individual PKC isoforms with regard to megakaryocyte differentiation and platelet production. However, the exact role of PKCepsilon remains elusive. OBJECTIVE: To delineate the role of PKCepsilon in megakaryopoiesis. APPROACH AND RESULTS: We used a PKCepsilon knockout mouse model to examine the effect of PKCepsilon deficiency on platelet mass, megakaryocyte mass, and bone marrow progenitor cell distribution. We also investigated platelet recovery in PKCepsilon null mice and TPO-mediated signaling in PKCepsilon null megakaryocytes. PKCepsilon null mice have higher platelet counts due to increased platelet production compared to WT littermate controls (p<0.05, n = 8). Furthermore, PKCepsilon null mice have more bone marrow megakaryocyte progenitor cells than WT littermate control mice. Additionally, thrombopoietin-mediated signaling is perturbed in PKCepsilon null mice as Akt and ERK1/2 phosphorylation are enhanced in PKCepsilon null megakaryocytes stimulated with thrombopoietin. Finally, in response to immune-induced thrombocytopenia, PKCepsilon null mice recovered faster and had higher rebound thrombocytosis than WT littermate control mice. CONCLUSIONS: Enhanced platelet recovery could be due to an increase in megakaryocyte progenitor cells found in PKCepsilon null mice as well as enhanced thrombopoietin-mediated signaling observed in PKCepsilon deficient megakaryocytes. These data suggest that PKCepsilon is a negative regulator of megakaryopoiesis. |
