MODULATION BY TGF-B1 OF HUMAN SCAR FIBROBLAST RECEPTORS

描述(改编自调查者摘要)：透明质酸是 增生性瘢痕增加，并已被证明影响 细胞分化。需要检验的假设是皮肤 成纤维细胞在功能上是不同的，创伤导致 对转化生长因子-β1反应能力改变的异常瘢痕成纤维细胞 和PDGF.具体目的是(1)确定表达式是否 转化生长因子-β1在正常和异常来源成纤维细胞中的表达差异 口腔面部瘢痕组织；(2)测定外源性转化生长因子-β1是否产生 正常和异常来源的成纤维细胞的激活差异 通过改变PDGF-α或-b受体的表达来调节组织；以及(3) 检查转化生长因子-β1是否调节透明质酸或 正常和异常来源成纤维细胞的透明质酸受体 疤痕组织以自分泌的方式。转化生长因子-β1的表达 在正常和异常皮肤的器官和细胞培养中进行检测。这个 转化生长因子-β1对PDGF受体和CD44(透明质酸受体)的影响 RNA和蛋白质将通过Northern blotts进行监测， 免疫细胞化学和放射免疫结合。转化生长因子-β1对血管内皮细胞生长的影响 透明质酸的合成也将在细胞中使用 放射性标记的透明质酸前体。

DESCRIPTION (adapted from the Investigator's abstract): Hyaluronan is increased in hypertrophic scarring and has been shown to influence cellular differentiation. The hypothesis to be tested is that cutaneous fibroblasts are functionally heterogeneous and that trauma gives rise to abnormal scar fibroblasts with altered capacity to respond to TGF-b1 and PDGF.The Specific Aims are to (1) determine whether the expression of TGF-b1 differs in fibroblasts derived from normal and abnormal orofacial scar tissues; (2) determine whether exogenous TGF-b1 produces differential activation of fibroblasts derived from normal vs. abnormal tissues by altering the expression of PDGF-alpha or -b receptors; and (3) examine whether TGF-b1 modulates the synthesis of either hyaluronan or hyaluronan receptors in fibroblasts derived from normal and abnormal scar tissues in an autocrine manner. The expression of TGF-b1 will be assayed in organ and cell cultures from normal and abnormal skin. The effects of TGF-b1 on PDGF receptors and CD44 (a hyaluronan receptor) mRNA and protein will be monitored by Northern blots, immunocytochemistry and radioimmunobinding. The effects of TGF-b1 on the synthesis of hyaluronan will also be monitored in cells using a radiolabeled hyaluronan precursor.