biostudies-literatureUnknown7(12)Racke FKThrombopoiesis following severe bone marrow injury frequently is delayed, thereby resulting in life-threatening thrombocytopenia for which there are limited treatment options. The reasons for these delays in recovery are not well understood. Protein kinase C (PKC) agonists promote megakaryocyte differentiation in leukemia cell lines and primary cells. However, little is known about the megakaryopoietic effects of PKC agonists on primary CD34+ cells grown in culture or in vivo. Here we present evidence that the novel PKC isoform-selective agonist 3,20 ingenol dibenzoate (IDB) potently stimulates early megakaryopoiesis of human CD34+ cells. In contrast, broad spectrum PKC agonists failed to do so. In vivo, a single intraperitoneal injection of IDB selectively increased platelets in mice withPloS onee51059https://www.ebi.ac.uk/biostudies/studies/S-EPMC3528756biostudies-literatureUnique in vitro and in vivo thrombopoietic activities of ingenol 3,20 dibenzoate, a Ca(++)-independent protein kinase C isoform agonist.PMC3528756Yang WRutledge HBaird MRacke FKBarth RFHuo TGupta NWeldon MfalseUnique in vitro and in vivo thrombopoietic activities of ingenol 3,20 dibenzoate, a Ca(++)-independent protein kinase C isoform agonist.Thrombopoiesis following severe bone marrow injury frequently is delayed, thereby resulting in life-threatening thrombocytopenia for which there are limited treatment options. The reasons for these delays in recovery are not well understood. Protein kinase C (PKC) agonists promote megakaryocyte differentiation in leukemia cell lines and primary cells. However, little is known about the megakaryopoietic effects of PKC agonists on primary CD34+ cells grown in culture or in vivo. Here we present evidence that the novel PKC isoform-selective agonist 3,20 ingenol dibenzoate (IDB) potently stimulates early megakaryopoiesis of human CD34+ cells. In contrast, broad spectrum PKC agonists failed to do so. In vivo, a single intraperitoneal injection of IDB selectively increased platelets in mice with2012-01-01T00:00:00Z20122025-05-31T22:54:17.491Z2025-05-31T22:54:17.491ZS-EPMC35287562328465710.1371/journal.pone.0051059