CYTOKINE-STIMULATED HUMAN VASCULAR SMOOTH-MUSCLE CELLS SYNTHESIZE A COMPLEMENT OF ENZYMES REQUIRED FOR EXTRACELLULAR-MATRIX DIGESTION
CYTOKINE-STIMULATED HUMAN VASCULAR SMOOTH-MUSCLE CELLS SYNTHESIZE A COMPLEMENT OF ENZYMES REQUIRED FOR EXTRACELLULAR-MATRIX DIGESTION
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DOI：
10.1161/01.res.75.1.181
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发表时间：
1994-07-01
影响因子：
20.1
通讯作者：
LIBBY, P
中科院分区：
文献类型：
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作者：
GALIS, ZS;MUSZYNSKI, M;LIBBY, P
血管基质重塑发生在发育、生长和影响血管的几种病理状况期间。我们研究了人平滑肌细胞（SMC）表达基质金属蛋白酶（MMPs）的能力，MMPs是一种选择性消化细胞外基质（ECM）成分的酶，在基础状态下或用某些与血管稳态和病理学有关的细胞因子刺激后。通过明胶或酪蛋白十二烷基硫酸钠-聚丙烯酰胺凝胶电泳酶谱法检测与培养基中分泌的各种蛋白相关的酶活性。通过免疫沉淀和北方印迹鉴定蛋白质和mRNA。SMC组成性分泌72 kD明胶酶和基质金属蛋白酶组织抑制剂（TIMPs）类型1和2。用白细胞介素-1或肿瘤坏死因子-α刺激的SMC重新合成92-kD明胶酶、间质胶原酶和基质溶解素。几条证据表明，当受到细胞因子刺激时，SMC产生活化形式的MMPs。组成型酶和精氨酸诱导的酶一起可以消化血管ECM的所有主要组分。此外，由于这些介质增加MMP的产生而不明显影响TIMP的合成，局部分泌的细胞因子可能会使MMP活性的区域平衡倾向于血管基质降解。
Vascular matrix remodeling occurs during development, growth, and several pathological conditions that affect blood vessels. We investigated the capacity of human smooth muscle cells (SMCs) to express matrix metalloproteinases (MMPs), enzymes that selectively digest components of the extracellular matrix (ECM), in the basal state or after stimulation with certain cytokines implicated in vascular homeostasis and pathology. Enzymatic activity associated with various proteins secreted in the culture media was detected by gelatin or casein sodium dodecyl sulfate-polyacrylamide gel electrophoresis zymography. Proteins were identified by immunoprecipitation and mRNA by Northern blotting. SMCs constitutively secreted a 72-kD gelatinase and the tissue inhibitors of MMPs (TIMPs) types 1 and 2. SMCs stimulated with interleukin-1 or tumor necrosis factor-alpha synthesized de novo 92-kD gelatinase, interstitial collagenase, and stromelysin. Several lines of evidence suggest that when stimulated by cytokines, SMCs produce activated forms of MMPs. Together, the constitutive and the cytokine-induced enzymes can digest all the major components of the vascular ECM. Moreover, since these mediators augment the production of MMPs without appreciably affecting the synthesis of TIMPs, locally secreted cytokines may tip the regional balance of MMP activity in favor of vascular matrix degradation.