The effect of TGF-beta on keloid fibroblast proliferation and collagen synthesis
The effect of TGF-beta on keloid fibroblast proliferation and collagen synthesis
复制标题
DOI：
10.1097/00006534-199610000-00012
复制
发表时间：
1996-10-01
影响因子：
3.6
通讯作者：
Cohen, IK
中科院分区：
文献类型：
--
作者：
Bettinger, DA;Yager, DR;Cohen, IK
瘢痕疙瘩的特点是过度丰富的胶原沉积，切除后经常复发。从瘢痕疙瘩组织分离并维持在细胞培养物中的成纤维细胞继续表达增加的产生胶原的能力。为了确定瘢痕疙瘩形成的机制，研究了外源性转化生长因子β（1）（TGF-β（1））对培养的瘢痕疙瘩或正常真皮来源的人成纤维细胞DNA合成和胶原蛋白表达的差异影响。在本研究中，发现浓度为5.0 ng/ml的TGF-β（1）刺激瘢痕疙瘩来源的成纤维细胞的DNA合成的程度大于正常真皮来源的成纤维细胞。通过微量测定胶原酶可消化的放射性标记蛋白质水平，发现与正常真皮来源的成纤维细胞相比，TGF-β 1在瘢痕疙瘩来源的成纤维细胞中引起绝对胶原合成的更大增加。tRNA（亲）池的具体活动的检查表明，这些观察到的胶原蛋白合成率的差异是不平等的脯氨酸运输率或池大小的结果。同样，TGF-β（1）也不会改变维生素C的摄取，维生素C是胶原蛋白最大表达所需的一种重要辅因子和介体。TGF-β（1）处理瘢痕疙瘩来源的成纤维细胞胶原合成的增加伴随着I型前胶原mRNA水平的相应增加，表明瘢痕疙瘩和正常皮肤成纤维细胞对这种生长因子的不同反应主要发生在翻译前水平。这些结果表明瘢痕疙瘩成纤维细胞对TGF-β 1具有独特的敏感性，因此这种介质在瘢痕疙瘩发病机制中可能发挥作用。
Keloids are characterized by an overabundant deposition of collagen, and they recur frequently following excision. Fibroblasts isolated from keloid tissue and maintained in cell culture continue to express an increased capacity to produce collagen. In an effort to define the mechanisms responsible for keloid formation, the potential of exogenous transforming growth factor beta(1) (TGF-beta(1)) to differentially affect DNA synthesis and collagen expression in cultured human fibroblasts derived from keloid or normal dermis was investigated. In this study, TGF-beta(1) at a concentration of 5.0 ng/ml was found to stimulate DNA synthesis of keloid-derived fibroblasts to a greater extent than fibroblasts derived from normal dermis. With a microassay to measure levels of collagenase-digestible radiolabeled proteins, TGF-beta(1) was found to elicit a greater increase in absolute collagen synthesis in keloid-derived fibroblasts compared with fibroblasts derived from normal dermis. Examination of tRNA(pro) pool-specific activities indicated that these observed differences in rates of collagen synthesis were not the result of unequal rates of proline transport or pool size. Likewise, TGF-beta(1) did not alter the uptake of vitamin C, an essential cofactor and mediator needed for maximal collagen expression. The increase in collagen synthesis by keloid-derived fibroblasts treated with TGF-beta(1) was accompanied by a corresponding increase in procollagen type I mRNA levels, indicating that the differential response of keloid and normal dermal fibroblasts to this growth factor is occurring primarily at a pretranslational level. These results suggest a unique sensitivity of keloid fibroblasts to TGF-beta(1) and thus a possible role for this mediator in keloid pathogenesis.