Abstract：OBJECTIVE: To investigate the role of spleen tyrosine kinase (Syk) in rat pulmonary vascular smooth muscle cells (PVSMCs) proliferation induced by platelet-derived growth factor-BB (PDGF-BB). METHODS: PVSMCs from male Sprague-Dawley rats were cultured in vitro and the cells of passages 3-5 were used in the experiment. PVSMCs were stimulated by PDGF-BB and were treated with three different doses of piceatannol, a Syk selective inhibitor. Cell proliferation was assessed by methyl thiazolyl tetrazolium (MTT) assay. DNA synthesis was measured by 3H-thymidine incorporation (3H-TdR). Cellular cycle was observed by flow cytometry. Syk mRNA and protein expression were detected using real-time quantitative PCR and Western blot, respectively. RESULTS: The expression of Syk protein of PVSMCs was significantly up-regulated following PDGF-BB stimulation. PDGF-BB stimulation dramatically increased PVSMCs proliferation. After piceatannol treatment, both Syk mRNA and protein expression decreased and the proliferation of PVSMCs was inhibited in a dose-dependent manner. CONCLUSIONS: Syk may promote PVSMCs proliferation induced by PDGF-BB.［Chin J Contemp Pediatr, 2010, 12 (11):886-890］
LUO Qin,GAO Zheng-Xiang,CAO Li-Li et al. Effect of spleen tyrosine kinase on the proliferation of pulmonary vascular smooth muscle cells in rats[J]. CJCP, 2010, 12(11): 886-890.
［1］Jeffery TK, Morrell NW. Molecular and cellular basis of vascular remodeling in pulmonary hypertension［J］. Prog Cardiovasc Dis, 2002, 45(3): 173-202.
［2］Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine［J］. Genes Dev, 2008, 22(10): 1276-1312.
［3］Lee CK, Lee HM, Kim HJ, Park HJ, Won KJ, Roh HY, et al. Syk contributes to PDGF-BB-mediated migration of rat aortic smooth muscle cells via MAPK pathways［J］. Cardio Res, 2007, 74(1): 159-168.
［4］Yaghini FA, Li F, Malik KU. Expression and mechanism of spleen tyrosine kinase activation by angiotensin ii and its implication in protein synthesis in rat vascular smooth muscle cells［J］. J Biol Chem, 2007, 282(23): 16878-16890.
［5］Sada K, Takano T, Yanagi S, Yamamura H. Structure and function of Syk proteintyrosine kinase［J］. J Biochem, 2001, 130(2): 177-186.
［6］Yanagi S, Inatome R, Takano T, Yamamura H. Syk expression and novel function in a wide variety of tissues［J］. Biochem Biophys Res Commun, 2001, 288(3): 495-498.
［7］Inatome R, Yanagi S, Takano T, Yamamura H. A critical role for Syk in endothelial cell proliferation and migration［J］. Biochem Biophys Res Commun, 2001, 286(1):195-199.
［8］Tsang F, Choo HH, Dawe GS, Wong WS. Inhibitors of the tyrosine kinase signaling cascade attenuated thrombin-induced guinea pig airway smooth muscle cell proliferation［J］. Biochem Biophys Res Commun, 2002, 293(1): 72-78.
［9］Moroni M, Soldatenkov V, Zhang L, Zhang Y, Stoica G, Gehan E, et al. Progressive loss of Syk and abnormal proliferation in breast cancer cells［J］. Cancer Res, 2004, 64(10): 7346-7354.
［10］Toyama T, Iwase H, Yamashita H, Hara Y, Omoto Y, Sugiura H, et al. Reduced expression of the Syk gene is correlated with poor prognosis in human breast cancer［J］. Cancer Lett, 2003, 189(1): 97-102.
［11］Coopman PJ, Do MT, Barth M, Bowden ET, Hayes AJ, Basyuk E, et al. The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells［J］. Nature, 2000, 406(6797): 742-747.
［12］Wang H, Malbon CC. G(s) alpha repression of adipogenesis via Syk［J］. J Biol Chem, 1999, 274(45): 32159-32166.
［13］Youssef LA, Wilson BS, Oliver JM. Proteasome-dependent regulation of Syk tyrosine kinase levels in human basophils［J］. J Allergy Clin Immunol, 2002, 110(3): 366-373.
［14］Kepley CL. Antigen-induced reduction in mast cell and basophil functional responses due to reduced Syk protein levels［J］. Int Arch Allergy Immunol, 2005, 138(1): 29-39.
