MODULATION BY TGF-B1 OF HUMAN SCAR FIBROBLAST RECEPTORS

描述（改编自研究者摘要）：Hybryonan是 增加增生性瘢痕，并已被证明影响 细胞分化。 待检验的假设是， 成纤维细胞在功能上是异质性的， 对TGF-β 1反应能力改变的异常瘢痕成纤维细胞 具体的目的是（1）确定表达是否 TGF-β 1在正常和异常成纤维细胞中的表达不同， 口面瘢痕组织;（2）确定外源性TGF-β 1是否产生 来源于正常与异常的成纤维细胞的差异活化 通过改变PDGF-α或-B受体的表达来治疗组织;和（3） 检查TGF-β 1是否调节透明质酸或 正常和异常成纤维细胞中透明质酸受体 疤痕组织以自分泌的方式。 TGF-β 1的表达将是 在来自正常和异常皮肤的器官和细胞培养物中测定。 的 TGF-β 1对PDGF受体和CD 44（透明质酸受体）的作用 通过北方印迹监测mRNA和蛋白质， 免疫细胞化学和放射免疫结合。 TGF-b1对 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.