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Thrombopoietin and collagen in low doses cooperatively induce human platelet activation

AIM: In acute medicine, we occasionally treat life‐threatening conditions such as sepsis and trauma, which cause severe thrombocytopenia. Serum thrombopoietin levels have been reported to increase under the condition of thrombocytopenia related to severity. Collagen is a crucial activator of platele...

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Autores principales: Doi, Tomoaki, Hori, Takamitsu, Onuma, Takashi, Mizutani, Daisuke, Ueda, Kyohei, Enomoto, Yukiko, Matsushima‐Nishiwaki, Rie, Tanabe, Kumiko, Hioki, Tomoyuki, Tokuda, Haruhiko, Iwama, Toru, Iida, Hiroki, Kozawa, Osamu, Ogura, Shinji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233307/
https://www.ncbi.nlm.nih.gov/pubmed/35782955
http://dx.doi.org/10.1002/ams2.769
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author Doi, Tomoaki
Hori, Takamitsu
Onuma, Takashi
Mizutani, Daisuke
Ueda, Kyohei
Enomoto, Yukiko
Matsushima‐Nishiwaki, Rie
Tanabe, Kumiko
Hioki, Tomoyuki
Tokuda, Haruhiko
Iwama, Toru
Iida, Hiroki
Kozawa, Osamu
Ogura, Shinji
author_facet Doi, Tomoaki
Hori, Takamitsu
Onuma, Takashi
Mizutani, Daisuke
Ueda, Kyohei
Enomoto, Yukiko
Matsushima‐Nishiwaki, Rie
Tanabe, Kumiko
Hioki, Tomoyuki
Tokuda, Haruhiko
Iwama, Toru
Iida, Hiroki
Kozawa, Osamu
Ogura, Shinji
author_sort Doi, Tomoaki
collection PubMed
description AIM: In acute medicine, we occasionally treat life‐threatening conditions such as sepsis and trauma, which cause severe thrombocytopenia. Serum thrombopoietin levels have been reported to increase under the condition of thrombocytopenia related to severity. Collagen is a crucial activator of platelets, and Rho family members, such as Rho/Rho‐kinase and Rac, play roles as active molecules involved in the intracellular signaling pathways in platelet activation. The present study aimed to elucidate the effects of thrombopoietin (TPO) on subthreshold low‐dose collagen‐stimulated human platelets in terms of Rho/Rho‐kinase and Rac. METHODS: Platelet‐rich plasma donated from healthy volunteers was stimulated by the subthreshold low‐dose of collagen after pretreatment with TPO and/or NSC23766, an inhibitor of the Rac‐guanine nucleotide exchange factor interaction, or Y27632, an inhibitor of Rho‐kinase. Platelet aggregation was measured using an aggregometer based on laser‐scattering methods. Proteins involved in intracellular signaling were analyzed using western blotting, and the secretion of platelet‐derived growth factor‐AB from activated platelets was determined using an enzyme‐linked immunosorbent assay. RESULTS: Under the existence of TPO, the low dose of collagen remarkably elicited the aggregation and platelet‐derived growth factor‐AB secretion of platelets, which were suppressed by NSC23766 and Y27632. The combination of TPO and collagen considerably induced a transient increase of guanosine triphosphate (GTP)‐binding Rac and GTP‐binding Rho followed by an increase of phosphorylated cofilin, a Rho‐kinase substrate. CONCLUSION: These results strongly suggest that TPO and collagen in low doses cooperatively potentiate human platelet activation through both Rac and Rho/Rho‐kinase mediated pathways.
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spelling pubmed-92333072022-06-30 Thrombopoietin and collagen in low doses cooperatively induce human platelet activation Doi, Tomoaki Hori, Takamitsu Onuma, Takashi Mizutani, Daisuke Ueda, Kyohei Enomoto, Yukiko Matsushima‐Nishiwaki, Rie Tanabe, Kumiko Hioki, Tomoyuki Tokuda, Haruhiko Iwama, Toru Iida, Hiroki Kozawa, Osamu Ogura, Shinji Acute Med Surg Original Articles AIM: In acute medicine, we occasionally treat life‐threatening conditions such as sepsis and trauma, which cause severe thrombocytopenia. Serum thrombopoietin levels have been reported to increase under the condition of thrombocytopenia related to severity. Collagen is a crucial activator of platelets, and Rho family members, such as Rho/Rho‐kinase and Rac, play roles as active molecules involved in the intracellular signaling pathways in platelet activation. The present study aimed to elucidate the effects of thrombopoietin (TPO) on subthreshold low‐dose collagen‐stimulated human platelets in terms of Rho/Rho‐kinase and Rac. METHODS: Platelet‐rich plasma donated from healthy volunteers was stimulated by the subthreshold low‐dose of collagen after pretreatment with TPO and/or NSC23766, an inhibitor of the Rac‐guanine nucleotide exchange factor interaction, or Y27632, an inhibitor of Rho‐kinase. Platelet aggregation was measured using an aggregometer based on laser‐scattering methods. Proteins involved in intracellular signaling were analyzed using western blotting, and the secretion of platelet‐derived growth factor‐AB from activated platelets was determined using an enzyme‐linked immunosorbent assay. RESULTS: Under the existence of TPO, the low dose of collagen remarkably elicited the aggregation and platelet‐derived growth factor‐AB secretion of platelets, which were suppressed by NSC23766 and Y27632. The combination of TPO and collagen considerably induced a transient increase of guanosine triphosphate (GTP)‐binding Rac and GTP‐binding Rho followed by an increase of phosphorylated cofilin, a Rho‐kinase substrate. CONCLUSION: These results strongly suggest that TPO and collagen in low doses cooperatively potentiate human platelet activation through both Rac and Rho/Rho‐kinase mediated pathways. John Wiley and Sons Inc. 2022-06-25 /pmc/articles/PMC9233307/ /pubmed/35782955 http://dx.doi.org/10.1002/ams2.769 Text en © 2022 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Doi, Tomoaki
Hori, Takamitsu
Onuma, Takashi
Mizutani, Daisuke
Ueda, Kyohei
Enomoto, Yukiko
Matsushima‐Nishiwaki, Rie
Tanabe, Kumiko
Hioki, Tomoyuki
Tokuda, Haruhiko
Iwama, Toru
Iida, Hiroki
Kozawa, Osamu
Ogura, Shinji
Thrombopoietin and collagen in low doses cooperatively induce human platelet activation
title Thrombopoietin and collagen in low doses cooperatively induce human platelet activation
title_full Thrombopoietin and collagen in low doses cooperatively induce human platelet activation
title_fullStr Thrombopoietin and collagen in low doses cooperatively induce human platelet activation
title_full_unstemmed Thrombopoietin and collagen in low doses cooperatively induce human platelet activation
title_short Thrombopoietin and collagen in low doses cooperatively induce human platelet activation
title_sort thrombopoietin and collagen in low doses cooperatively induce human platelet activation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233307/
https://www.ncbi.nlm.nih.gov/pubmed/35782955
http://dx.doi.org/10.1002/ams2.769
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