Growth factor and cytokine modulation of trabecular meshwork matrix metalloproteinase and TIMP expression
Growth factor and cytokine modulation of trabecular meshwork matrix metalloproteinase and TIMP expression
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DOI：
10.1076/ceyr.17.3.276.5219
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发表时间：
1998-03-01
影响因子：
2
通讯作者：
Acott, TS
中科院分区：
文献类型：
--
作者：
Alexander, JP;Samples, JR;Acott, TS
目的.我们假设，由基质金属蛋白酶启动的调节性小梁细胞外基质（ECM）周转对于维持正常的房水流出率至关重要。然而，很少有人知道小梁细胞外基质周转的调节。为了鉴定候选的小梁调节因子，我们评估了几种生长因子和细胞因子对小梁基质金属蛋白酶和TIMP表达的影响。用几种剂量的各种生长和细胞因子处理猪小梁网细胞，并在24、48和72 h后分析培养基。采用酶谱法检测基质分解素、明胶酶A和B活性水平，采用免疫印迹法检测基质分解素、胶原酶、TIMP-1和TIMP-2蛋白水平。佛波醇有丝分裂原（TPA）、TNF α和β、白细胞介素-1 α和PDGF BE刺激明胶酶B、基质溶解素、间质胶原酶和TIMP-1表达，同时对明胶酶A表达具有可忽略的影响，TIMP-2水平被TNF降低，但不受其他治疗的影响。酸性和碱性FGF、IL-1 β、TGF β和PDGF AB产生类似但较小的作用，而HGF、VEGF、EGF、KGF和LIF产生小至中度的基质溶解素升高，而其他反应最小。PDGF AA、γ INF抑瘤素-M和内皮素-1对这些蛋白酶和转运蛋白的影响可以忽略不计。除了提供调节小梁金属蛋白酶和TIMP水平的潜在方法外，这些细胞对这些生长因子和细胞因子中的一些的反应性表明在正常或致病性小梁细胞调节中可能起作用，并且一些可能影响房水流出。
Purpose. We hypothesize that regulated trabecular extracellular matrix (ECM) turnover, initiated by the matrix metalloproteinases, is critical for the maintenance of normal aqueous humor outflow rates. However, very little is known about the regulation of trabecular ECM turnover. To identify candidate trabecular regulators, we evaluated the effects of several growth factors and cytokines on trabecular matrix metalloproteinase and TIMP expression.Methods. Porcine trabecular meshwork cells were treated with several doses of a variety of growth and cytokines and culture media was analyzed after 24, 48 and 72 h. Zymograms were used to evaluate stromelysin, gelatinase A and B activity levels, while immunoblots of Western transfers were used to evaluate stromelysin, collagenase, TIMP-1 and TIMP-2 protein levels.Results. A phorbol mitogen (TPA), TNF alpha and beta, interleukin-1 alpha and PDGF BE stimulate gelatinase B, stromelysin, interstitial collagenase and TIMP-1 expression, while having negligible effects on gelatinase A expression, TIMP-2 levels are reduced by TNF but not affected by the other treatments. Acidic and basic FGF, IL-1 beta, TGF beta and PDGF AB produce similar but smaller effects, while HGF, VEGF, EGF, KGF and LIF produce small to moderate elevations in stromelysin with minimal other responses. PDGF AA, gamma INF oncostatin-M and endothelin-1 produce negligible changes in these proteinases and inhibitors.Conclusions. In addition to providing potential ways to modulate trabecular metalloproteinase and TIMP levels, the responsiveness of these cells to some of these growth factors and cytokines suggests possible roles in normal or pathogenic trabecular cell regulation and some may affect aqueous humor outflow.