Stromelysin and tissue inhibitor of metalloproteinases gene expression in rheumatoid arthritis synovium.
Stromelysin and tissue inhibitor of metalloproteinases gene expression in rheumatoid arthritis synovium.
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发表时间：
1992-06
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通讯作者：
G. Firestein;M. M. Paine-M.
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作者：
G. Firestein;M. M. Paine-M.
应用原位杂交技术对类风湿关节炎滑膜组织中基质分解素mRNA进行定位。基质分解素反义探针主要与冷冻组织切片中的内膜衬里层杂交，几乎没有或没有衬里下层信号。基质溶解素的表达与细胞结构相关，通过与肌动蛋白探针杂交确定。采用双标记法同时检测滑膜组织中基质分解素和金属蛋白酶组织抑制剂（TIMP）mRNA的表达。在内膜衬里细胞亚群中鉴定了两种mRNA的共表达。在一些高度炎症的组织中，几乎所有的衬里细胞都与两种探针杂交。然而，在其他组织中，这两种基因的表达是不一致的，有大量的TIMP阳性/基质溶解素（阴性）细胞。用晚期传代培养的滑膜细胞观察到类似的结果。未受刺激的细胞不表达基质分解素基因，而TIMP是组成性产生的。向培养物中加入白细胞介素-1 β（IL-1 β）或肿瘤坏死因子-α（TNF-α）诱导前者，但对后者几乎没有影响。双标记实验清楚地显示了单个细胞中的不一致表达。基质分解素和TIMP基因可能具有不同的转录控制，其提供对局部环境和基质周转的精确控制。
In situ hybridization was used to localize stromelysin mRNA in rheumatoid arthritis synovial tissue. Stromelysin antisense probes hybridized primarily to the intimal lining layer in frozen tissue sections, with little or no sublining signal. The expression of stromelysin correlated with cellularity as determined by hybridization with an actin probe. Double-label experiments were performed to detect tissue inhibitor of metalloproteinases (TIMP) and stromelysin mRNA simultaneously in synovial tissue. Coexpression of both mRNA species was identified in a subpopulation of intimal lining cells. In some highly inflammatory tissues, virtually all of the lining cells hybridized to both probes. However, in other tissues, expression of the two genes was discordant, with large numbers of TIMPpositive/stromelysin(negative) cells. Similar results were observed with late-passage cultured synoviocytes. Unstimulated cells did not express the stromelysin gene, whereas TIMP was constitutively produced. Addition of interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) to cultures induced the former but had little effect on the latter. Double-label experiments clearly showed discordant expression in individual cells. Stromelysin and TIMP genes likely have distinct transcriptional controls that provide precise control over the local environment and matrix turnover.