beta-Tryptase up-regulates vascular endothelial growth factor expression via proteinase-activated receptor-2 and mitogen-activated protein kinase pathways in bone marrow stromal cells in acute myeloid leukemia.
Tryptases are predominantly mast cell-specific serine proteases with pleiotropic biological activities. Recently, significant amounts of tryptases have been shown to be produced by myeloblasts in certain patients with acute myeloid leukemia (AML), but the function of secreted tryptases in pathological circumstances remains unknown. In this study, we investigated whether beta-tryptase affects the expression of vascular endothelial growth factor (VEGF) in bone marrow stromal cells (BMSCs) in AML. We detected the expression of proteinase-activated receptor-2 (PAR-2) on AML BMSCs and found that beta-tryptase significantly up-regulated VEGF mRNA and protein expression in a dose-dependent manner by real-time PCR, Western blot, and ELISA. Furthermore, beta-tryptase increased ERK1/2 and p38MAPK phosphorylation, and pretreatment with FLLSY-NH(2), PD98059, and SB230580 (PAR-2, ERK1/2, and p38MAPK inhibitors, respectively) inhibited the beta-tryptase-induced production of VEGF. These results suggest that beta-tryptase up-regulates VEGF production in AML BMSCs via the PAR-2, ERK1/2, and p38MAPK signaling pathways.
Yang
Xiu-Peng
XP
Department of Hematology, First Affiliated Hospital of China Medical University, Shenyang, China.
Li
Yan
Y
Wang
Yazhu
Y
Wang
Yue
Y
Wang
Pingping
P
D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D053802:Tryptases / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D044464:Receptor, PAR-2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020928:Mitogen-Activated Protein Kinases; D053802:Tryptases