Stanniocalcin-1 Is an Ocular Hypotensive Agent and a Downstream Effector Molecule That Is Necessary for the Intraocular Pressure-Lowering Effects of Latanoprost.
Stanniocalcin-1 Is an Ocular Hypotensive Agent and a Downstream Effector Molecule That Is Necessary for the Intraocular Pressure-Lowering Effects of Latanoprost.
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Stanniocalcin-1 是一种降眼压剂，也是拉坦前列素降低眼压作用所必需的下游效应分子。
DOI：
10.1167/iovs.16-21004
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发表时间：
2017
影响因子：
4.4
通讯作者：
Fautsch,MichaelP
中科院分区：
文献类型：
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作者：
Roddy,GavinW;Viker,KimberlyB;Winkler,NelsonS;Bahler,CindyK;Holman,BradleyH;Sheikh-Hamad,David;RoyChowdhury,Uttio;Stamer,WDaniel;Fautsch,MichaelP
目的：为了确定下游信号分子，通过该分子眼内压（IOP）降低治疗后的前列腺素类似物latanoprost.Methods：总RNA和蛋白质分离的主要人Schlemm氏管细胞（n= 3）处理拉坦前列素（游离酸; 100 nM）进行定量PCR和蛋白质印迹分析。在拉坦前列素或Rho激酶抑制剂Y27632治疗后，在斯钙素-1（STC-1−/−）和野生型小鼠中评价IOP。用重组STC-1（5、50或500 ng/mL）处理人眼前节对（n= 8），并使用定制设计的软件记录压力。在野生型小鼠中评估重组STC-1（0.5mg/mL）对IOP的影响。组织形态进行了评价，通过光和透射电子显微镜。结果：增加STC-1 mRNA（4.0- 25.2倍）和蛋白质表达（1.9- 5.1倍），观察拉坦前列素治疗后12小时内。拉坦前列素降低野生型小鼠的IOP（22.0%±1.9%），但对STC-1−/−小鼠无影响（0.5%±0.7%）。相比之下，Y27632降低了野生型（12.5%±1.2%）和STC-1−/−小鼠（13.1%±2.8%）的IOP。用STC-1（500 ng/mL）处理的人眼前节显示出流出功能的增加（0.15±0.03至0.27±0.09 μL/min/mm Hg），而在配对的溶媒处理对照中未观察到变化。重组STC-1使野生型小鼠的IOP降低15.2%± 3.0%。没有观察到的形态学变化，确定治疗组之间进行评估时，通过microscopic.Conclusions：拉坦前列素诱导的IOP降低是通过下游信号分子STC-1介导的。当单独使用时，STC-1表现出眼部扩张特性。
Purpose: To identify downstream signaling molecules through which intraocular pressure (IOP) is lowered following treatment with the prostaglandin analog latanoprost.Methods: Total RNA and protein isolated from primary human Schlemm's canal cells (n= 3) treated with latanoprost (free acid; 100 nM) were processed for quantitative PCR and Western blot analysis. IOP was evaluated in stanniocalcin-1 (STC-1−/−) and wild-type mice following treatment with latanoprost or Rho kinase inhibitor Y27632. Human anterior segment pairs (n= 8) were treated with recombinant STC-1 (5, 50, or 500 ng/mL) and pressure was recorded using custom-designed software. The effect of recombinant STC-1 (0.5 mg/mL) on IOP was evaluated in wild-type mice. Tissue morphology was evaluated by light and transmission electron microscopy.Results: Increased STC-1 mRNA (4.0-to 25.2-fold) and protein expression (1.9-to 5.1-fold) was observed within 12 hours following latanoprost treatment. Latanoprost reduced IOP in wild-type mice (22.0%±1.9%), but had no effect on STC-1−/− mice (0.5%±0.7%). In contrast, Y27632 reduced IOP in both wild-type (12.5%±1.2%) and in STC-1−/− mice (13.1%±2.8%). Human anterior segments treated with STC-1 (500 ng/mL) showed an increase in outflow facility (0.15±0.03 to 0.27±0.09 μL/min/mm Hg) while no change was observed in paired vehicle-treated controls. Recombinant STC-1 reduced IOP in wild-type mice by 15.2%±3.0%. No observable morphologic changes were identified between treatment groups when evaluated by microscopy.Conclusions: Latanoprost-induced reduction of IOP is mediated through the downstream signaling molecule STC-1. When used by itself, STC-1 exhibits ocular hypotensive properties.