AIM To study the effects of TGF-β1 on the plasminogen activation (PA) system of stem cells from the apical papilla (SCAP) and its signalling. METHODOLOGY SCAP cells were isolated from the apical papilla of immature permanent teeth extracted for orthodontic reasons. They were exposed to various concentration of TGF-β1 with/without pretreatment and coincubation by SB431542 (ALK/Smad2/3 inhibitor), or U0126 (MEK/ERK inhibitor). MTT assay, Western blotting and enzyme-linked immunosorbent assay (ELISA) were used to detect their effects on cell viability, and the protein expression of plasminogen activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and their secretion. The paired Student's t-test was used for statistical analysis. RESULTS TGF-β1 significantly stimulated PAI-1 and soluble uPAR (suPAR) secretion of SCAP cells (P < 0.05), whereas uPA secretion was inhibited. Accordingly, TGF-β1 induced both PAI-1 and uPAR protein expression of SCAP cells. SB431542 (an ALK5/Smad2/3 inhibitor) pretreatment and coincubation prevented the TGF-β1-induced PAI-1 and uPAR of SCAP. U0126 attenuated the TGF-β1-induced expression/secretion of uPAR, but not PAI-1 in SCAP. SB431542 reversed the TGF-β1-induced decline of uPA. CONCLUSIONS TGF-β1 may affect the repair/regeneration activities of SCAP via differential increase or decrease of PAI-1, uPA and uPAR. These effects induced by TGF-β1 are associated with ALK5/Smad2/3 and MEK/ERK activation. Elucidation the signalling pathways and effects of TGF-β1 is useful for treatment of immature teeth with open apex by revascularization/revitalization procedures and tissue repair/regeneration.

中文翻译：

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转化生长因子-β1对根尖乳头干细胞中纤溶酶原激活的影响：激活受体样激酶5 / Smad2和有丝分裂原激活的蛋白激酶激酶（MEK）/细胞外信号调节激酶（ERK）信号传导的作用。

目的研究TGF-β1对根尖乳头（SCAP）干细胞的纤溶酶原激活（PA）系统及其信号传导的影响。方法学从正畸原因的未成熟恒牙的根尖乳头中分离出SCAP细胞。通过/不通过SB431542（ALK / Smad2 / 3抑制剂）或U0126（MEK / ERK抑制剂）进行预处理和共孵育，将它们暴露于各种浓度的TGF-β1。使用MTT法，蛋白质印迹法和酶联免疫吸附法（ELISA）检测它们对细胞存活率的影响，以及纤溶酶原激活物抑制剂-1（PAI-1），尿激酶型纤溶酶原激活物（uPA），uPA的蛋白表达。受体（uPAR）及其分泌。配对的学生t检验用于统计分析。结果TGF-β1显着刺激SCAP细胞的PAI-1和可溶性uPAR（suPAR）分泌（P <0.05），而uPA分泌受到抑制。因此，TGF-β1诱导SCAP细胞的PAI-1和uPAR蛋白表达。SB431542（ALK5 / Smad2 / 3抑制剂）的预处理和共孵育可防止TGF-β1诱导的SCAP的PAI-1和uPAR。U0126减弱了SCAP中TGF-β1诱导的uPAR的表达/分泌，但不减弱PAI-1。SB431542逆转了TGF-β1诱导的uPA下降。结论TGF-β1可能通过PAI-1，uPA和uPAR的差异性升高或降低来影响SCAP的修复/再生活性。TGF-β1诱导的这些作用与ALK5 / Smad2 / 3和MEK / ERK激活有关。