METALLOPROTEINASES AND TISSUE INHIBITOR OF METALLOPROTEINASES IN MESOTHELIAL CELLS - CELLULAR-DIFFERENTIATION INFLUENCES EXPRESSION
METALLOPROTEINASES AND TISSUE INHIBITOR OF METALLOPROTEINASES IN MESOTHELIAL CELLS - CELLULAR-DIFFERENTIATION INFLUENCES EXPRESSION
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DOI：
10.1172/jci116390
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发表时间：
1993-04-01
影响因子：
15.9
通讯作者：
WELGUS, HG
中科院分区：
文献类型：
--
作者：
MARSHALL, BC;SANTANA, A;WELGUS, HG
间皮细胞在浆膜损伤后的重塑过程中起关键作用。虽然已知间皮细胞合成多种细胞外基质成分，包括I、III和IV型胶原，但它们参与基质降解的潜力尚未被探索。我们现在报道，人胸膜和腹膜间皮细胞表达间质胶原酶、72-和92-kD明胶酶(IV型胶原酶)，以及金属蛋白酶的逆调控组织抑制物(TIMP)。我们对间皮细胞金属酶和TIMP的初步表征揭示：(A)它们可能与其他人类细胞分泌的相应分子相同；(B)它们是分泌的，而不是储存在细胞内池中；(C)主要的调控位点发生在翻译前水平；(D)佛波酯通过激活蛋白激酶C上调胶原酶、92-kD明胶酶和TIMP的表达，但对72-kD明胶酶的表达没有影响；(E)脂多糖不能上调金属蛋白酶或TIMP的生物合成。特别有趣的是，观察到细胞分化状态对金属酶和TIMP的表达有显著影响，因此上皮样细胞表现出比成纤维样细胞更多的基质降解表型(92-kD明胶酶增加，TIMP减少)。我们推测间皮细胞通过金属蛋白酶和TIMP的表达直接参与浆膜损伤后细胞外基质的转化。此外，反应性立方体间皮细胞是浆膜损伤早期反应的特征，可能表现为一种基质降解的表型，有利于正常修复而不是纤维化。
Mesothelial cells play a critical role in the remodeling process that follows serosal injury. Although mesothelial cells are known to synthesize a variety of extracellular matrix components including types I, III, and IV collagens, their potential to participate in matrix degradation has not been explored. We now report that human pleural and peritoneal mesothelial cells express interstitial collagenase, 72- and 92-kD gelatinases (type IV collagenases), and the counterregulatory tissue inhibitor of metalloproteinases (TIMP). Our initial characterization of the mesothelial cell metalloenzymes and TIMP has revealed: (a) they are likely identical to corresponding molecules secreted by other human cells; (b) they are secreted rather than stored in an intracellular pool; (c) a primary site of regulation occurs at a pretranslational level; (d) phorbol myristate acetate, via activation of protein kinase C, upregulates expression of collagenase, 92-kD gelatinase, and TIMP, but has no effect on expression of 72-kD gelatinase; and (e) lipopolysaccharide fails to upregulate the biosynthesis of either metalloproteinases or TIMP. Of particular interest is the observation that the state of cellular differentiation has a striking influence on the expression of metalloenzymes and TIMP, such that epithelioid cells display a more matrix-degradative phenotype (increased 92-kD gelatinase and decreased TIMP) than their fibroblastoid counterparts. We speculate that mesothelial cells directly participate in the extracellular matrix turnover that follows serosal injury via elaboration of metalloproteinases and TIMP. Additionally, the reactive cuboidal mesothelium which is characteristic of the early response to serosal injury may manifest a matrix-degradative phenotype favoring normal repair rather than fibrosis.