REGULATION OF CONNECTIVE-TISSUE GROWTH-FACTOR GENE-EXPRESSION IN HUMAN SKIN FIBROBLASTS AND DURING WOUND REPAIR
REGULATION OF CONNECTIVE-TISSUE GROWTH-FACTOR GENE-EXPRESSION IN HUMAN SKIN FIBROBLASTS AND DURING WOUND REPAIR
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DOI：
10.1091/mbc.4.6.637
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发表时间：
1993-06-01
影响因子：
3.3
通讯作者：
GROTENDORST, GR
中科院分区：
文献类型：
--
作者：
IGARASHI, A;OKOCHI, H;GROTENDORST, GR
结缔组织生长因子（CTGF）是一种富含半胱氨酸的多肽，具有血小板源性生长因子（PDGF）样生物学和免疫学活性。CTGF是一个肽家族的成员，该家族包括血清诱导的立即早期基因产物、v-src诱导的肽和推定的禽类转化基因nov。在本研究中，我们证明了人包皮成纤维细胞在转化生长因子β激活后产生高水平的CTGF mRNA和蛋白在一些实施方案中，细胞生长因子包括TGF-β，但不包括其他生长因子，包括PDGF、表皮生长因子和碱性成纤维细胞生长因子。由于TGF-β对CTGF的高水平选择性诱导，CTGF似乎是由TGF-β处理的人皮肤成纤维细胞产生的主要自分泌生长因子。放线菌酮没有阻断CTGF基因表达的大的TGF-β刺激，表明它直接受TGF-β调节。类似的调节机制似乎在伤口修复期间在体内起作用，其中在再生组织中在CTGF之前存在TGF-β 1的协调表达，这表明用于控制组织再生和修复的级联过程。
Connective tissue growth factor (CTGF) is a cysteine-rich peptide that exhibits platelet-derived growth factor (PDGF)-like biological and immunological activities. CTGF is a member of a family of peptides that include serum-induced immediate early gene products, a v-src-induced peptide, and a putative avian transforming gene, nov. In the present study, we demonstrate that human foreskin fibroblasts produce high levels of CTGF mRNA and protein after activation with transforming growth factor beta (TGF-beta) but not other growth factors including PDGF, epidermal growth factor, and basic fibroblast growth factor. Because of the high level selective induction of CTGF by TGF-beta, it appears that CTGF is a major autocrine growth factor produced by TGF-beta-treated human skin fibroblasts. Cycloheximide did not block the large TGF-beta stimulation of CTGF gene expression, indicating that it is directly regulated by TGF-beta. Similar regulatory mechanisms appear to function in vivo during wound repair where there is a coordinate expression of TGF-beta1 before CTGF in regenerating tissue, suggesting a cascade process for control of tissue regeneration and repair.