A unifying hypothesis for the renin-angiotensin system and hematopoiesis: sticking the pieces together with the JAK-STAT pathway.

JAK-STAT pathway is a recently encountered intracellular signal transduction system. The pathway is utilized by numerous cytokines, growth factors, and hormones for gene expression and a variety of biological activities. Hematopoiesis is regulated by many cytokines and growth factors that support the proliferation and differentiation of progenitor cells in the bone marrow. JAK-STAT pathway arises as the most common signalling cascade of a wide range of cytokines and/or growth factors in propagation of physiological and pathological/neoplastic hematopoiesis. On the other side, renin-angiotensin system (RAS) includes not only the classic circulating endocrine system controlling blood pressure and electrolyte homeostasis, but also tissue-specific RASs with autocrine and/or paracrine functions. Preliminary data suggest the involvement of the RAS components in normal and pathologic hematopoiesis, although the precise mechanism of action has not been elucidated yet. We have hypothesized, in this report, that JAK-STAT pathway serves as a point of crosstalk between the components of the locally present RAS in the bone marrow and hematopoiesis. Demonstration of a local RAS in the bone marrow with clarification of the postreceptor signalling events may play a consequential role not only for further clarification of normal hematopoiesis but also novel therapeutic approaches in pathologic/neoplastic conditions.