Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis

Sci Rep. 2017 Jul 27;7(1):6684. doi: 10.1038/s41598-017-07096-w.


Megakaryocytopoiesis is a complex differentiation process driven by the hormone thrombopoietin by which haematopoietic progenitor cells give rise to megakaryocytes, the giant bone marrow cells that in turn break down to form blood platelets. The Tribbles Pseudokinase 3 gene (TRIB3) encodes a pleiotropic protein increasingly implicated in the regulation of cellular differentiation programmes. Previous studies have hinted that TRIB3 could be also involved in megakaryocytopoiesis but its role in this process has so far not been investigated. Using cellular model systems of haematopoietic lineage differentiation here we demonstrate that TRIB3 is a negative modulator of megakaryocytopoiesis. We found that in primary cultures derived from human haematopoietic progenitor cells, thrombopoietin-induced megakaryocytic differentiation led to a time and dose-dependent decrease in TRIB3 mRNA levels. In the haematopoietic cell line UT7/mpl, silencing of TRIB3 increased basal and thrombopoietin-stimulated megakaryocyte antigen expression, as well as basal levels of ERK1/2 phosphorylation. In primary haematopoietic cell cultures, silencing of TRIB3 facilitated megakaryocyte differentiation. In contrast, over-expression of TRIB3 in these cells inhibited the differentiation process. The in-vitro identification of TRIB3 as a negative regulator of megakaryocytopoiesis suggests that in-vivo this gene could be important for the regulation of platelet production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Line
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Silencing / drug effects
  • Humans
  • Megakaryocytes / cytology
  • Megakaryocytes / drug effects
  • Megakaryocytes / metabolism*
  • Phosphorylation / drug effects
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Thrombopoiesis* / drug effects
  • Thrombopoietin / pharmacology


  • Cell Cycle Proteins
  • RNA, Messenger
  • Repressor Proteins
  • TRIB3 protein, human
  • Thrombopoietin
  • Protein Serine-Threonine Kinases
  • Extracellular Signal-Regulated MAP Kinases