The Role of Vasoactive Intestinal Peptide (VIP) in Megakaryocyte Proliferation

Journal of Molecular Neuroscience (Impact Factor: 2.34). 02/2009; 37(2):160-167. DOI: 10.1007/s12031-008-9119-x


Megakaryocytopoiesis is a multistage process that involves differentiation of hematopoietic stem cells through the myeloid
lineage, ultimately producing megakaryocytes and platelets. Vasoactive intestinal peptide (VIP) stimulates adenylate cyclase
and induces differentiation in multiple cell types; VIP is expressed in hematopoietic stem cells and in megakaryocytes, but
its function in these cells has not yet been delineated. The present study was designed to investigate whether the type 1
VIP receptor, VPAC1, mediates VIP effects on megakaryocytopoiesis. The human megakaryoblastic leukemia cell line (CMK) was
transfected with VPAC1 and the transgene expression was confirmed by qualitative polymerase chain reaction and immunohistochemistry.
The rate of proliferation and the patterns of differentiation were then compared for CMK and CMK/VPAC1 through multiple growth
cycles. Upregulation of VPAC1 expression resulted in a decreased proliferation rate (p = 0.0003) and enhanced differentiation with CMK/VPAC1 cells having twice the cell surface area of control CMK cells (p = 0.001), thus increasing potential for proplatelet formation. These results suggest that VIP acts in an autocrine fashion
via VPAC1 to inhibit megakaryocyte proliferation and induce proplatelet formation.

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