Stimulatory Effects of Hepatocyte Growth Factor on Hemopoiesis of SCF/c‐kit System‐Deficient Mice

Abstract

In this study, we report that W/W mutant mice, which have severe macrocytic anemia caused by a deficit of extracellular domain in c-kit molecules and therefore die perinatally, have hemopoietic stem cells (HSCs) and mature hematolymphoid cells in the bone marrow (BM), thymus, and spleen, although there are significant decreases in cell counts. Moreover, the mitogen-induced proliferative response, mixed lymphocyte reaction, and anti-SRBC plaque formation of spleen cells in W/W mice are similar to those in age-matched +/? littermates and normal mice, suggesting that the SCF/c-kit system is necessary for cell proliferation but not essential for HSCs to differentiate.We next examine the stimulatory effects of hepatocyte growth factor (HGF) on hemopoiesis in W/W mice. HGF has a stimulatory effect on the colony formation These results suggest that the SCF/c-kit system is not essential to hemopoiesis but that a compensatory system such as the HGF/c-met system functions in the SCF/c-kit system-deficient mice.

DrosophilaRel proteins are central regulators of a robust, multi-organ immune network

“…Just as Rel protein activity in the Drosophila fat body provides factors that promote survival or proliferation of blood cells, the mammalian liver (the analogue of the fat body) secretes growth factors such as the hepatic growth factor (HGF) and interleukin-7 that act as survival and proliferation molecules for blood cells (Sawa et al, 2009;Sugiura et al, 2007;Yu et al, 1998), although it is not known whether Rel proteins directly regulate their production.…”

A recombinant single-chain IL-7/HGFβ hybrid cytokine induces juxtacrine interactions of the IL-7 and HGF (c-Met) receptors and stimulates the proliferation of CFU-S12, CLPs, and pre-pro-B cells

“…[22][23][24] HGF has been reported to regulate hematopoiesis in mouse fetal liver and adult bone marrow, where it apparently can substitute for the stem cell factor (SCF) and c-kit system. 25,26 However, its role in the regulation of lymphopoiesis is unclear. [27][28][29] Therefore, it is of interest that the IL-7/HGF␤ hybrid cytokine was found to selectively induce proliferation and differentiation of pre-pro-B cells in rat BM, and, by up-regulating IL-7R␣ chain and c expression, to enable pro-B cells to respond to monomeric IL-7.…”

Mitogenic synergy through multilevel convergence of hepatocyte growth factor and interleukin-4 signaling pathways

“…Erythropoietin (EPO) and HGF also act synergistically to induce the formation of erythroid burst-forming unit colonies from CD34 + HPC (Ikehara, 1996;Iguchi et al, 1999). HGF compensates for de®ciencies in stem cell proliferation observed in mice harboring dominant mutations in the genes encoding stem cell factor (SCF) or its receptor, ckit (Yu et al, 1998). HGF enhances antibody production in mature B cells (Delaney et al, 1993), and stimulates rapid cytoskeletal changes, adhesion, and migration in peripheral blood T cells (Adams et al, 1994).…”