Activation of Janus kinase/signal transducers and activators of transcription pathway involved in megakaryocyte proliferation induced by vanadium resembles some aspects of essential thrombocythemia

作者：Gonzalez Villalva Adriana^*; Pinon Zarate Gabriela; Falcon Rodriguez Carlos; Lopez Valdez Nelly; Bizarro Nevares Patricia; Rojas Lemus Marcela; Rendon Huerta Erika; Colin Barenque Laura; Fortoul Teresa I

来源：Toxicology and Industrial Health, 2016, 32(5): 908-918.

DOI：10.1177/0748233713518600

• Vanadium
• megakaryocytes
• platelets
• JAK
• STAT pathway
• Mpl
• essential thrombocythemia

Vanadium (V) is an air pollutant released into the atmosphere by burning fossil fuels. Also, it has been recently evaluated for their carcinogenic potential to establish permissible limits of exposure at workplaces. We previously reported an increase in the number and size of platelets and their precursor cells and megakaryocytes in bone marrow and spleen. The aim of this study was to identify the involvement of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway and thrombopoietin (TPO) receptor, and myeloproliferative leukemia virus oncogene (Mpl), in megakaryocyte proliferation induced by this compound. Mice were exposed twice a week to vanadium pentoxide inhalation (0.02 M) and were killed at 4th, 6th, and 8th week of exposure. Phosphorylated JAK2 (JAK2 ph), STAT3 (STAT3 ph), STAT5, and Mpl were identified in mice spleen megakaryocytes by cytofluorometry and immunohistochemistry. An increase in JAK2 ph and STAT3 ph, but a decrease in Mpl at 8-week exposure was identified in our findings. Taking together, we propose that the morphological findings, JAK/STAT activation, and decreased Mpl receptor induced by V leads to a condition comparable to essential thrombocythemia, so the effect on megakaryocytes caused by different mechanisms is similar. We also suggest that the decrease in Mpl is a negative feedback mechanism after the JAK/STAT activation. Since megakaryocytes are platelet precursors, their alteration affects platelet morphology and function, which might have implications in hemostasis as demonstrated previously, so it is important to continue evaluating the effects of toxics and pollutants on megakaryocytes and platelets.

• 出版日期2016-5