Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor
Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor
复制标题
DOI：
10.1111/1523-1747.ep12363389
复制
发表时间：
1996-09-01
影响因子：
6.5
通讯作者：
Grotendorst, GR
中科院分区：
文献类型：
--
作者：
Frazier, K;Williams, S;Grotendorst, GR
结缔组织生长因子（CTGF）是一种36- 38 kda的肽，可由转化生长因子- β (tgf - β)在成纤维细胞类型中选择性诱导。我们比较了CTGF和tgf - β在培养成纤维细胞和纤维增生动物模型中的生物活性。在正常大鼠肾成纤维细胞单层培养中，CTGF作为有丝分裂原具有活性，但CTGF不刺激NRK成纤维细胞的非锚定生长，也不抑制水貂肺上皮细胞的生长，这与tgf - β的生长调节活性不同。在NRK成纤维细胞中，tgf - β和CTGF均显著增加编码α 1型胶原、α 5整合素和纤维连接蛋白的转录本。用[S-35]蛋氨酸脉冲标记细胞，证实tgf - β和CTGF刺激I型胶原和纤维连接蛋白合成。新生NIH瑞士小鼠皮下注射tgf - β和CTGF可引起注射部位肉芽组织的大量刺激和纤维化。原位杂交研究发现，tgf - β注射可诱导注射部位真皮成纤维细胞中高水平的CTGF mRNA表达，表明tgf - β在体内可诱导结缔组织细胞中CTGF的表达。在对照组或注射tgf - β皮肤的表皮细胞中，或在注射盐水的对照组皮肤的成纤维细胞中，均未检测到CTGF转录本。这些结果表明，与tgf - β一样，CTGF可以诱导结缔组织细胞增殖和细胞外基质合成。
Connective tissue growth factor (CTGF) is a 36- to 38-kDa peptide that is selectively induced by transforming growth factor-beta (TGF-beta) in fibroblastic cell types, We compared the biologic activities of CTGF with TGF-beta on fibroblasts in culture and in animal models of fibroplasia. CTGF was active as a mitogen in monolayer cultures of normal rat kidney fibroblasts, CTGF did not stimulate anchorage-independent growth of NRK fibroblasts, however, or inhibit the growth of mink lung epithelial cells, distinguishing CTGF's growth-regulatory activities from those of TGF-beta. In NRK fibroblasts, both TGF-beta and CTGF significantly increased the transcripts encoding alpha 1 type I collagen, alpha 5 integrin, and fibronectin. Stimulation of type I collagen and fibronectin protein synthesis by TGF-beta and CTGF was confirmed by pulse labeling of cells with [S-35]methionine. Subcutaneous injection of TGF-beta and CTGF into neonatal NIH Swiss mice resulted in a large stimulation of granulation tissue and fibrosis at the site of injection. lit situ hybridization studies revealed that TGF-beta injection induced high levels of CTGF mRNA in the dermal fibroblasts at the injection site, demonstrating that TGF-beta can induce the expression of CTGF in connective tissue cells in vivo. No CTGF transcripts mere detected in the epidermal cells in either control or TGF-beta-injected skin or in fibroblasts in control (saline-injected) skin. These results demonstrate that, like TGF-beta, CTGF can induce connective tissue cell proliferation and extracellular matrix synthesis.