COLLAGEN-SYNTHESIS BY HUMAN-FIBROBLASTS - REGULATION BY TRANSFORMING GROWTH FACTOR-BETA IN THE PRESENCE OF OTHER INFLAMMATORY MEDIATORS
COLLAGEN-SYNTHESIS BY HUMAN-FIBROBLASTS - REGULATION BY TRANSFORMING GROWTH FACTOR-BETA IN THE PRESENCE OF OTHER INFLAMMATORY MEDIATORS
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DOI：
10.1042/bj2600463
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发表时间：
1989-06-01
影响因子：
4.1
通讯作者：
SWANSON, J
中科院分区：
文献类型：
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作者：
NARAYANAN, AS;PAGE, RC;SWANSON, J
我们已经检查了转化生长因子-β的联合作用。（TGF-β），血清和γ-干扰素（γ- IFN）对成纤维细胞胶原合成的影响，并比较成纤维细胞亚群对TGF-β的反应。用TGF-β处理人二倍体成纤维细胞。单独和与血清或γ-的IFN用放射性氨基酸标记细胞，并以胶原酶可消化的放射性来测量胶原蛋白的产生。使用前胶原-α 1 [I] cDNA克隆HF 677通过溶液杂交测定来测定胶原mRNA。结果显示，血清或TGF-β均能抑制肿瘤细胞增殖。通过成纤维细胞增加掺入、胶原蛋白产生和mRNA。2倍;然而，相对于总蛋白质合成胶原合成和相对于总聚腺苷酸化[poly（A）+] RNA的胶原mRNA不受影响。只有血清激活细胞生长。胶原蛋白产量增加约。4-在暴露于TGF-β和TGF-β的细胞中，和血清中，并且该增加等于两种组分的加和效应的预期增加。用γ处理IFN减少胶原蛋白的产生和胶原蛋白mRNA的44和40%，分别，而总掺入和聚（A）+ RNA的影响只有轻微的。细胞同时暴露于两种γ- IFN和TGF-β。与用TGF-β处理的那些相比，产生更少的胶原和含有更少的mRNA。一个人γ- IFN减少对照中的胶原合成，TGF-β-以相似程度处理培养物，并且TGF-β.在用γ-葡聚糖预处理的细胞中胶原蛋白合成增加2倍的IFN在含有源自血浆的血清的培养基中获得的成纤维细胞染色合成的胶原蛋白大约是在新鲜人血清和TGF-β存在下源自相同外植体的细胞合成的胶原蛋白的一半。在两种细胞株中刺激胶原蛋白产生和mRNA。我们推断TGF-β，血清和γ- IFN通过独立的机制调节胶原合成，并且这些组分的组合作用在伤口愈合和组织修复期间调节胶原合成中起重要作用。
We have examined the combined effects of transforming growth factor-.beta. (TGF-.beta.), serum and .gamma.-interferon (.gamma.-IFN) on collagen synthesis by fibroblasts and compared the response of fibroblast subpopulations to TGF-.beta.. Human diploid fibroblasts were treated with TGF-.beta. alone and with serum or .gamma.-IFN. Cells were labelled with radioactive amino acids, and collagen production was measured as collagenase-digestible radioactivity. Collagen mRNA was determined by a solution-hybridization assay using procollagen-.alpha.1[I] cDNA clone HF 677. The results showed that either serum or TGF-.beta. increased incorporation, collagen production and mRNA by fibroblasts approx. 2-fold; however, collagen synthesis relative to total protein synthesis and collagen mRNA relative to total polyadenylated [poly (A)+] RNA were not affected. Only serum activated cell growth. Collagen production increased approx. 4-fold in cells exposed to both TGF-.beta. and serum, and this increase was equal to that expected for an additive effect by both components. Treatment with .gamma.-IFN decreased collagen production and collagen mRNA to 44 and 40%, respectively, whereas total incorporation and poly(A)+ RNA were affected only marginally. Cells exposed simultaneously to both .gamma.-IFN and TGF-.beta. produced less collagen and contained less mRNA than did those treated with TGF-.beta. alone. The .gamma.-IFN decreased collagen synthesis in control and TGF-.beta.-treated cultures to a similar extent, and TGF-.beta. increased collagen synthesis 2-fold in cells pre-treated with .gamma.-IFN. Fibroblast stains obtained in medium containing plasma-derived serum synthesized approximately half as much collagen as did cells derived from the same explant in the presence of fresh human serum, and TGF-.beta. stimulated collagen production and mRNA in both cell strains. We conclude that TGF-.beta., serum and .gamma.-IFN regulate collagen synthesis by independent mechanisms, and that the combined action of these components plays a significant role in regulating collagen synthesis during wound healing and tissue repair.