Pentland A P
Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri 63110.
J Cell Physiol. 1989 May;139(2):392-7. doi: 10.1002/jcp.1041390223.
Fibroblasts are routinely maintained in vitro on tissue culture plastic, in an environment which is devoid of collagen, the most abundant extracellular protein in dermis. Recent work has shown that by seeding fibroblasts into a collagen matrix, many aspects of their metabolism change dramatically: they stop proliferation, organize and contract the collagen matrix, and secrete much larger quantities of the usual extracellular matrix components. Because so many fibroblast functions are dramatically altered by the presence of the collagen matrix, matrix effects on fibroblast metabolism of arachidonic acid were examined. The studies presented here show that during the period of matrix contraction, metabolism of arachidonate to prostaglandins by fibroblasts is increased sixfold compared to cells plated on plastic, and that this increase is correlated with contraction but does not regulate it. The increase in prostaglandin synthesis is due in part to an increased new synthesis of the rate-limiting enzyme in prostaglandin synthesis, cyclooxygenase. No change in the profile of products the fibroblasts synthesize from arachidonate is induced by the presence of the matrix. After the lattice contraction is complete, the basal arachidonate metabolism of matrix-embedded cells have the same capacity to synthesize PGE2 in response to IL-1 as do cells grown on plastic. However, the response to the hormone agonist bradykinin by the matrix-embedded cells is present on day 1 but not on day 3, the time when cells grown on plastic are most responsive. These data indicate that while basal prostaglandin metabolism is unaffected in quiescent fibroblasts which have been embedded in a collagen matrix, response to hormone agonists may be greatly attenuated. The changes in the metabolism of arachidonate which occur during the process of matrix contraction and organization may play a part in the regulation of wound repair.
成纤维细胞通常在组织培养塑料上进行体外培养，所处环境中没有胶原蛋白，而胶原蛋白是真皮中最丰富的细胞外蛋白质。最近的研究表明，将成纤维细胞接种到胶原蛋白基质中后，其代谢的许多方面会发生显著变化：它们停止增殖，组织并收缩胶原蛋白基质，并分泌大量通常的细胞外基质成分。由于胶原蛋白基质的存在会使成纤维细胞的许多功能发生显著改变，因此研究了基质对成纤维细胞花生四烯酸代谢的影响。此处呈现的研究表明，在基质收缩期间，与接种在塑料上的细胞相比，成纤维细胞将花生四烯酸代谢为前列腺素的能力增加了六倍，且这种增加与收缩相关，但并不调节收缩。前列腺素合成的增加部分归因于前列腺素合成限速酶环氧化酶的新合成增加。基质的存在并未诱导成纤维细胞从花生四烯酸合成的产物谱发生变化。在晶格收缩完成后，嵌入基质的细胞的基础花生四烯酸代谢在响应白细胞介素-1时合成前列腺素E2的能力与在塑料上生长的细胞相同。然而，嵌入基质的细胞对激素激动剂缓激肽的反应在第1天存在，但在第3天不存在，而在塑料上生长的细胞在第3天反应最为强烈。这些数据表明，虽然嵌入胶原蛋白基质的静止成纤维细胞的基础前列腺素代谢未受影响，但对激素激动剂的反应可能会大大减弱。在基质收缩和组织化过程中发生的花生四烯酸代谢变化可能在伤口修复的调节中起作用。
