differential role of gp130-dependent stat and ras signalling for haematopoiesis following bone-marrow transplantation微分作用gp130-dependent统计和ras信号对骨髓移植后造血作用.pdfVIP

Differential Role of gp130-Dependent STAT and Ras Signalling for Haematopoiesis Following Bone-Marrow Transplantation 1 1 1,4 2 1 1 Daniela C. Kroy , Lisa Hebing , Leif E. Sander , Nikolaus Gassler , Stephanie Erschfeld , Sara Sackett , 3 1 1 Oliver Galm , Christian Trautwein , Konrad L. Streetz * 1 Department of Medicine III, University Hospital Aachen, Aachen, Germany, 2 Institute of Pathology, University Hospital Aachen, Aachen, Germany, 3 Department of ´ Medicine IV, University Hospital Aachen, Aachen, Germany, 4 Department of Infectious Diseases and Pulmonary Medicine, Charite University Hospital Berlin, Berlin, Germany Abstract Introduction: Bone marrow transplantation (BMT) is a complex process regulated by different cytokines and growth factors. The pleiotropic cytokine IL-6 (Interleukin-6) and related cytokines of the same family acting on the common signal transducer gp130 are known to play a key role in bone marrow (BM) engraftment. In contrast, the exact signalling events that control IL-6/gp130-driven haematopoietic stem cell development during BMT remain unresolved. Methods: Conditional gp130 knockout and knockin mice were used to delete gp130 expression (gp130DMx), or to selectively disrupt gp130-dependent Ras (gp130DMxRas) or STAT signalling (gp130DMxSTAT) in BM cells. BM derived from the respective strains was transplanted into irradiated wildtype hosts and repopulation of various haematopoietic lineages was monitored by flow c