Megakaryocytic Maturation in Response to Shear Flow Is Mediated by the Activator Protein 1 (AP-1) Transcription Factor via Mitogen-activated Protein Kinase (MAPK) Mechanotransduction.

The Journal of Biological Chemistry
Stephanie A Luff, Eleftherios T Papoutsakis

Abstract

Megakaryocytes (MKs) are exposed to shear flow as they migrate from the bone marrow hematopoietic compartment into circulation to release pro/preplatelets into circulating blood. Shear forces promote DNA synthesis, polyploidization, and maturation in MKs, and platelet biogenesis. To investigate mechanisms underlying these MK responses to shear, we carried out transcriptional analysis on immature and mature stem cell-derived MKs exposed to physiological shear. In immature (day (d)9) MKs, shear exposure up-regulated genes related to growth and MK maturation, whereas in mature (d12) MKs, it up-regulated genes involved in apoptosis and intracellular transport. Following shear-flow exposure, six activator protein 1 (AP-1) transcripts (ATF4,JUNB,JUN,FOSB,FOS, andJUND) were up-regulated at d9 and two AP-1 proteins (JunD and c-Fos) were up-regulated both at d9 and d12. We show that mitogen-activated protein kinase (MAPK) signaling is linked to both the shear stress response and AP-1 up-regulation. c-Jun N-terminal kinase (JNK) phosphorylation increased significantly following shear stimulation, whereas JNK inhibition reduced shear-induced JunD expression. Although p38 phosphorylation did not increase following shear flow, its inhibitio...Continue Reading

References

Jul 14, 1995·The Journal of Biological Chemistry·M Karin
Nov 1, 1995·Calcified Tissue International·R L Duncan, C H Turner
Oct 1, 1996·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·A J Whitmarsh, R J Davis
May 23, 1998·Arteriosclerosis, Thrombosis, and Vascular Biology·O Traub, B C Berk
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·S Y FuchsZ Ronai
Dec 21, 2000·American Journal of Physiology. Heart and Circulatory Physiology·N AzumaB E Sumpio
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·V G TusherG Chu
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·B L BennettD W Anderson
Sep 24, 2002·Seminars in Cell & Developmental Biology·Sarah M King, Guy L Reed
Dec 4, 2002·Journal of Cellular Biochemistry·Fred M PavalkoJoseph P Bidwell
Jan 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·He YangE Terry Papoutsakis
Feb 20, 2003·The Journal of Cell Biology·Murray C H ClarkeSimon B Brown
Mar 5, 2003·BioTechniques·A I SaeedJ Quackenbush
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·J E Italiano, R A Shivdasani
Dec 12, 2003·Nature Reviews. Cancer·Robert Eferl, Erwin F Wagner
Jun 10, 2004·Microbiology and Molecular Biology Reviews : MMBR·Philippe P Roux, John Blenis
Nov 27, 2004·Journal of Cell Science·Jochen HessMarina Schorpp-Kistner
Sep 17, 2005·Journal of Cellular Biochemistry·Song LiSteven Hsu
Oct 15, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Dardo E FerraraW Robert Taylor
Aug 22, 2006·Developmental Biology·Sagar DamleScott E Fraser
Aug 31, 2006·Methods in Enzymology·Alexander I SaeedJohn Quackenbush
Aug 1, 2007·Journal of Thrombosis and Haemostasis : JTH·Y ChangW Vainchenker
Sep 22, 2007·Science·Tobias JuntUlrich H von Andrian
Jan 29, 2008·Blood·Kenneth Kaushansky
Apr 7, 2009·The Journal of Biological Chemistry·Jean François DumasEric Fontaine
Jun 16, 2009·Blood·Claire Dunois-LardéDominique Baruch
Jul 1, 2009·The Journal of Cell Biology·Jennifer C Waters
Jul 25, 2009·Nature Reviews. Cancer·Erwin F Wagner, Angel R Nebreda
Sep 17, 2009·The Journal of Biological Chemistry·Sun Taek KimEllis L Reinherz
Oct 31, 2009·Journal of Thrombosis and Haemostasis : JTH·S SéverinA Mazharian
Apr 12, 2011·Annals of Biomedical Engineering·Zhong-Dong Shi, John M Tarbell
Jun 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jae-Won ShinDennis E Discher

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Jan 31, 2020·Journal of Thrombosis and Haemostasis : JTH·Bhanu Kanth ManneMatthew T Rondina
Oct 6, 2021·Nature Communications·Kangsan KimSrinivas Malladi
Nov 4, 2021·Current Osteoporosis Reports·Blayne A SarazinMaureen E Lynch

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