Marinides G N, Suchard S J, Mookerjee B K
Department of Medicine, Dept. of Veterans' Affairs Medical Center, Buffalo, New York.
Kidney Int. 1994 Aug;46(2):350-7. doi: 10.1038/ki.1994.281.
Thrombospondin (TSP) is an extracellular matrix glycoprotein involved in mesangial cell (MC) adhesive and migratory function. We have studied the role of TSP in activation and proliferation of rat MC in serum-free media. TSP, in a concentration dependent manner (5 to 20 micrograms/ml), caused an increase in thymidine uptake, first detectable at 28 hours and more prominent at 48 hours. This effect was inhibited by heparin and heparan sulfate. TSP induced epidermal growth factor (EGF) secretion and significantly augmented constitutive platelet-derived growth factor-AB (PDGF-AB) secretion by MC in a concentration dependent fashion. It did not, however, induce TGF-beta, IL-1, IL-6, IL-8, or TNF-alpha production. TSP had an additive effect with exogenous EGF and PDGF on thymidine uptake. Anti-PDGF neutralizing antibody eliminated the effect of TSP on MC growth. MC displayed a single class of heparin-inhibitable TSP binding sites (Bmax 3.8 +/- 1.8 x 10(6)/cell, Kd = 80 +/- 29 nM). Based on these observations, we propose the existence of an autocrine positive feedback loop of MC proliferation involving TSP and growth factors, and regulated by heparan sulfate.
血小板反应蛋白（TSP）是一种细胞外基质糖蛋白，参与系膜细胞（MC）的黏附和迁移功能。我们研究了TSP在无血清培养基中对大鼠MC激活和增殖的作用。TSP以浓度依赖的方式（5至20微克/毫升）导致胸苷摄取增加，最早在28小时可检测到，在48小时时更为显著。这种作用被肝素和硫酸乙酰肝素抑制。TSP诱导表皮生长因子（EGF）分泌，并以浓度依赖的方式显著增加MC组成型血小板衍生生长因子-AB（PDGF-AB）的分泌。然而，它不诱导TGF-β、IL-1、IL-6、IL-8或TNF-α的产生。TSP对外源性EGF和PDGF在胸苷摄取方面具有相加作用。抗PDGF中和抗体消除了TSP对MC生长的作用。MC显示出一类单一的肝素抑制性TSP结合位点（Bmax 3.8 +/- 1.8 x 10(6)/细胞，Kd = 80 +/- 29 nM）。基于这些观察结果，我们提出存在一个涉及TSP和生长因子的MC增殖自分泌正反馈环，并受硫酸乙酰肝素调节。
