C3G, through its GEF activity, induces megakaryocytic differentiation and proplatelet formation
| Autor: | Cristina Baquero, Almudena Porras, Sara Gutiérrez-Herrero, Carmen Guerrero, Juan José Roldán-Etcheverry, José M. de Pereda, Cristina Fernández-Infante, Luis Hernández-Cano, Eduardo Anguita, Sara Ortiz-Rivero, Víctor Martín-Granado |
|---|---|
| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Junta de Castilla y León, European Commission |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
2407 Biología Celular lcsh:Medicine Biochemistry 0302 clinical medicine Megakaryocyte Platelet Adipogenesis lcsh:Cytology Chemistry Cell Differentiation 2411.08 Metabolismo Humano Cell biology Haematopoiesis medicine.anatomical_structure diferenciación celular 030220 oncology & carcinogenesis Differentiation Megakaryocytes Blood Platelets biología celular Bone Marrow Cells biología molecular 03 medical and health sciences Megakaryopoiesis plaquetas Cell Line Tumor medicine Humans Platelet activation lcsh:QH573-671 Molecular Biology Guanine Nucleotide-Releasing Factor 2 Thrombopoietin 2302.21 Biología Molecular Ploidies 2407.01 Cultivo Celular Research lcsh:R células de la médula ósea C3G Cell Biology 030104 developmental biology Bone marrow 2401.10 Histología Animal |
| Zdroj: | GREDOS. Repositorio Institucional de la Universidad de Salamanca instname Cell Communication and Signaling : CCS Cell Communication and Signaling, Vol 16, Iss 1, Pp 1-17 (2018) Digital.CSIC. Repositorio Institucional del CSIC Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid Digital.CSIC: Repositorio Institucional del CSIC Consejo Superior de Investigaciones Científicas (CSIC) GREDOS: Repositorio Institucional de la Universidad de Salamanca Universidad de Salamanca (USAL) |
| Popis: | [Background]: Megakaryopoiesis allows platelet formation, which is necessary for coagulation, also playing an important role in different pathologies. However, this process remains to be fully characterized. C3G, an activator of Rap1 GTPases, is involved in platelet activation and regulates several differentiation processes. [Methods]: We evaluated C3G function in megakaryopoiesis using transgenic mouse models where C3G and C3GΔCat (mutant lacking the GEF domain) transgenes are expressed exclusively in megakaryocytes and platelets. In addition, we used different clones of K562, HEL and DAMI cell lines with overexpression or silencing of C3G or GATA-1. [Results]: We found that C3G participates in the differentiation of immature hematopoietic cells to megakaryocytes. Accordingly, bone marrow cells from transgenic C3G, but not those from transgenic C3GΔCat mice, showed increased expression of the differentiation markers CD41 and CD61, upon thrombopoietin treatment. Furthermore, C3G overexpression increased the number of CD41+ megakaryocytes with high DNA content. These results are supported by data obtained in the different models of megakaryocytic cell lines. In addition, it was uncovered GATA-1 as a positive regulator of C3G expression. Moreover, C3G transgenic megakaryocytes from fresh bone marrow explants showed increased migration from the osteoblastic to the vascular niche and an enhanced ability to form proplatelets. Although the transgenic expression of C3G in platelets did not alter basal platelet counts, it did increase slightly those induced by TPO injection in vivo. Moreover, platelet C3G induced adipogenesis in the bone marrow under pathological conditions. [Conclusions]: All these data indicate that C3G plays a significant role in different steps of megakaryopoiesis, acting through a mechanism dependent on its GEF activity. This work was supported by grants from the Spanish Ministry of Economy and Competitiveness [SAF2013–48210-C2–1-R and SAF2016–76588-C2–2-R to CG, SAF2013–48210-C2–2-R and SAF2016–76588-C2–1-R to AP], and by two grants from the Council of Education of Junta de Castilla y León, Spain [SA157A12–1 and SA017U16 to CG]. All funding was cosponsored by the European FEDER Program. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|