TRANSFORMING GROWTH FACTOR-BETA-1 SELECTIVELY AUGMENTS COLLAGEN-SYNTHESIS BY HUMAN INTESTINAL SMOOTH-MUSCLE CELLS
TRANSFORMING GROWTH FACTOR-BETA-1 SELECTIVELY AUGMENTS COLLAGEN-SYNTHESIS BY HUMAN INTESTINAL SMOOTH-MUSCLE CELLS
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DOI：
10.1016/0016-5085(90)91028-5
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发表时间：
1990-08-01
期刊：
影响因子：
29.4
通讯作者：
DIEGELMANN, RF
中科院分区：
文献类型：
--
作者：
GRAHAM, MF;BRYSON, GR;DIEGELMANN, RF
肠平滑肌细胞通过增殖和产生胶原蛋白，在使慢性肠道炎症复杂化的狭窄形成中发挥重要作用。转化生长因子β 1已被鉴定为人体组织对炎症的纤维化反应中的重要炎症介质。为了确定该介质是否可能参与肠纤维化，在体外研究了转化生长因子β 1对人肠平滑肌细胞的胶原蛋白产生和增殖的影响。将第二代细胞在含有10% Nu-Serum（Collaborative Research Inc.，贝德福德，MA），之后降低Nu-Serum的浓度。48小时后，向培养基中加入转化生长因子β 1以达到1-500 pmol/L的浓度。暴露于转化生长因子β 1 24小时后，通过[3 H]脯氨酸摄取到胶原酶敏感蛋白中来测定细胞胶原合成。转化生长因子β 1引起每个细胞的胶原蛋白产量增加100%，非胶原蛋白产量增加40%，反映相对胶原蛋白合成增加58%。这种效应在10 pmol/L浓度下最大。相比之下，表皮生长因子对相对胶原合成没有显著影响。转化生长因子β 1在10 pmol/L时引起细胞对甲基氨基异丁酸（一种未代谢的氨基酸类似物）的摄取显著增加。然而，与在该浓度下对脯氨酸摄取到胶原中的影响（增加100%）相比，该影响较小（增加20%）。当通过[3 H]胸苷的摄取检查细胞增殖时，转化生长因子β 1没有影响，而表皮生长因子（1000 pmol/L）引起94%的增加。转化生长因子β 1在体外选择性地增加人肠平滑肌细胞的胶原蛋白产生。这种作用是有效的，并且与对细胞增殖或氨基酸摄取的作用无关。这些数据表明，转化生长因子β 1作为炎症介质在肠纤维化的发病机制中具有重要作用。
Intestinal smooth muscle cells play a major role in the stricture formation that complicates chronic intestinal inflammation, by proliferating and producing collagen. Transforming growth factor .beta.1 has been identified as an important inflammatory mediator in the fibrotic response of human tissue to inflammation. To determine whether this mediator might be involved in intestinal fibrosis, the effect of transforming growth factor .beta.1 on collagen production and proliferation by human intestinal smooth muscle cells was studied in vitro. Cells in the second passage were grown to subconfluence in medium containing 10% Nu-Serum (Collaborative Research Inc., Bedford, MA), after which the concentration of Nu-Serum was decreased. Forty-eight hours later, transforming growth factor .beta.1 was added to the culture medium to achieve concentrations of 1-500 pmol/L. After 24 hours exposure to the transforming growth factor .beta.1, cellular collagen synthesis was determined by the uptake of [3H]proline into collagenase-sensitive protein. Transforming growth factor .beta.1 caused a 100% increase in collagen production and a 40% increase in noncollagen protein production per cell, reflecting an increase in relative collagen synthesis of 58%. This effect was maximal at a concentration of 10 pmol/L. Epidermal growth factor, by comparison, had no significant effect on relative collagen synthesis. Transforming growth factor .beta.1 caused a significant increase in the uptake of methylaminoisobutyric acid, a nonmetabolized amino acid analog, into the cells at 10 pmol/L. However, this effect was small (20% increase) compared with the effect on the uptake of proline into collagen (100% increase) at this concentration. When cell proliferation was examined by the uptake of [3H]thymidine, transforming growth factor .beta.1 had no effect, whereas epidermal growth factor (1000 pmol/L) caused a 94% increase. Transforming growth factor .beta.1 selectively augments collagen production by human intestinal smooth muscle cells in vitro. This effect is potent and is not related to effects on either cell proliferation or amino acid uptake. These data suggest that transforming growth factor .beta.1 has an important role as an inflammatory mediator in the pathogenesis of intestinal fibrosis.