The effect of transforming growth factor-beta on cell proliferation and collagen formation by lung fibroblasts.

The effect of transforming growth factor-beta on cell proliferation and collagen formation by lung fibroblasts.
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DOI:
10.1016/s0021-9258(18)61441-3
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发表时间:
1987-03
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
A. Fine;R. Goldstein
A. Fine;R. Goldstein
中科院分区:
其他
文献类型:
--
作者:
A. Fine;R. Goldstein

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我们研究了转化生长因子- β (tgf - β)对人胚胎肺成纤维细胞培养的胶原蛋白产生的影响。与总蛋白的产生相比,tgf - β在0.1 ng/ml时似乎可以选择性地激活细胞外胶原的积累。在成纤维细胞培养中,当剂量为1.0 ng/ml时,诱导胶原蛋白和总蛋白产量增加2-3倍的最大效果。tgf - β暴露24和48小时后对成纤维细胞增殖没有影响,包括24小时后接受第二次剂量的培养物。tgf - β处理和未经处理的培养物中放射标记的胶原的胶原酶消化显示羟基化程度没有差异(37.3%对33.4%)。tgf - β增加了I型和III型胶原蛋白的产生,但不影响胶原蛋白类型的比例。在含有tgf - β的培养基中培养的成纤维细胞在至少72小时内保持了5 nmol/ml/24 h的胶原生成激活率。我们发现表皮生长因子略微增强了tgf - β诱导的胶原形成,而tgf - β增加了表皮生长因子的增殖作用。综上所述,这些数据表明胶原生成和细胞增殖可以独立调节,tgf - β可能通过刺激成纤维细胞来源的胶原合成在组织损伤的解决中发挥作用。
We examined the effects of transforming growth factor-beta (TGF-beta) on the production of collagen by cultures of human embryonic lung fibroblasts. TGF-beta at 0.1 ng/ml appeared to activate selectively extracellular collagen accumulation as compared with total protein production. A maximal effect inducing a 2-3-fold increase in collagen and total protein production occurred at a dose of 1.0 ng/ml in fibroblast cultures. TGF-beta had no effect on fibroblast proliferation after a 24- and 48-h exposure, including cultures that received a second dose after 24 h. Collagenase digestion of radiolabeled collagen derived from TGF-beta-treated and -untreated cultures revealed no differences in the extent of hydroxylation (37.3 versus 33.4%). TGF-beta increased the production of types I and III collagen without affecting the proportion of collagen types. Fibroblast cultures maintained in medium containing TGF-beta sustained an activated rate of collagen production of 5 nmol/ml/24 h over at least 72 h. We found that epidermal growth factor slightly enhanced TGF-beta-induced collagen formation, whereas TGF-beta increased the proliferative effect of epidermal growth factor. Taken together, these data indicate that collagen production and cell proliferation can be independently regulated and that TGF-beta may have a role in the resolution of tissue injury by stimulating fibroblast-derived collagen synthesis.