Prostaglandins increase proMMP-1 and proMMP-3 secretion by human ciliary smooth muscle cells
Prostaglandins increase proMMP-1 and proMMP-3 secretion by human ciliary smooth muscle cells
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DOI：
10.3109/02713689609017628
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发表时间：
1996-08-01
影响因子：
2
通讯作者：
Weinreb, RN
中科院分区：
文献类型：
--
作者：
Lindsey, JD;Kashiwagi, K;Weinreb, RN
目的。前列腺素 (PG)F-2 α 增加灵长类动物葡萄膜巩膜流出和降低眼内压的机制尚不清楚。在培养的人睫状肌细胞中，PGF(2α) 诱导原癌基因 c-fos 的表达，已知该基因可诱导其他细胞系统中基质金属蛋白酶-1 (MMP-1) 和 MMP-3 等基因的转录。由于这些酶最初是作为酶原分泌的，因此本研究旨在确定 PG 治疗是否诱导睫状肌细胞分泌 proMMP-1 或 proMMP-3。 方法。将人睫状平滑肌细胞在单层鳗鱼培养物中生长至汇合，然后用 PGF(2 α)、17-苯基三去甲-PGF(2 α) 或 11-脱氧-PGE(1) 处理。使用夹心 ELISA 测定处理后不同时间收获的培养基的 proMMP-1 和 proMMP-3 含量。结果。添加10 nM PGF(2α)、proMMP-1 和pro-MMP-3 三天后，培养基中的浓度分别增加了254 +/- 33%（平均值+/- SE）和128 +/- 13%。与载体对照相比，用 200 nM PGF(2 α)、17-苯基三去甲-PGF(2 α) 或 PGE(1) 治疗 24 小时，proMMP-1 分别增加 116 +/- 29%、169 +/- 26% 和 273 +/- 16%。在平行实验中，proMMP-3 分别增加了 99 +/- 18%、82 +/- 24% 和 214 +/- 16%。 结论。这些结果表明，局部 PG 治疗后原位诱导 MMP 可能会降解睫状肌细胞外基质，并可能导致葡萄膜巩膜流出增加。
Purpose. The mechanism by which prostaglandin(PG)F-2 alpha increases uveoscleral outflow and lowers intraocular pressure in primates is not known. In cultured human ciliary muscle cells, PGF(2 alpha) induces the expression of the protooncogene c-fos which is known to induce the transcription of genes such as matrix metalloproteinase-1 (MMP-1) and MMP-3 in other cell systems. As these enzymes are initially secreted as proenzymes, the present study was undertaken to determine if PG treatment induces ciliary muscle cells to secrete either proMMP-1 or proMMP-3.Methods. Human ciliary smooth muscle cells were grown to confluence in monolayer eel cultures and then treated with PGF(2 alpha), 17-phenyltrinor-PGF(2 alpha), or 11-deoxy-PGE(1). Medium harvested at various times after treatment was assayed for proMMP-1 and proMMP-3 content using sandwich ELISAs.Results. Three days after adding 10 nM PGF(2 alpha), proMMP-1 and pro-MMP-3, concentrations in the culture medium were increased by 254 +/- 33% (mean +/- SE) and 128 +/- 13%, respectively. Compared with vehicle controls, 24 h treatment with 200 nM PGF(2 alpha), 17-phenyltrinor-PGF(2 alpha), or PGE(1), increased proMMP-1 by 116 +/- 29%, 169 +/- 26%, and 273 +/- 16%, respectively. In parallel experiments, proMMP-3 was increased by 99 +/- 18%, 82 +/- 24%, and 214 +/- 16%, respectively.Conclusions. These results suggest that induction of MMPs in situ following topical PG treatment may degrade ciliary muscle extracellular matrix and possibly contribute to increased uveoscleral outflow, as well.