Frazier K, Williams S, Kothapalli D, Klapper H, Grotendorst G R
Department of Cell Biology and Anatomy, University of Miami School of Medicine, FL 33136, USA.
J Invest Dermatol. 1996 Sep;107(3):404-11. doi: 10.1111/1523-1747.ep12363389.
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 [35S]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. In 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 were 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.
结缔组织生长因子（CTGF）是一种36至38 kDa的肽，在成纤维细胞类型中由转化生长因子-β（TGF-β）选择性诱导产生。我们比较了CTGF与TGF-β在培养的成纤维细胞和纤维化动物模型中的生物学活性。CTGF在正常大鼠肾成纤维细胞的单层培养中作为有丝分裂原具有活性。然而，CTGF不刺激NRK成纤维细胞的非贴壁依赖性生长，也不抑制貂肺上皮细胞的生长，这将CTGF的生长调节活性与TGF-β的生长调节活性区分开来。在NRK成纤维细胞中，TGF-β和CTGF均显著增加了编码α1 I型胶原、α5整合素和纤连蛋白的转录本。用[35S]甲硫氨酸对细胞进行脉冲标记证实了TGF-β和CTGF对I型胶原和纤连蛋白蛋白合成的刺激作用。将TGF-β和CTGF皮下注射到新生NIH瑞士小鼠体内，导致注射部位的肉芽组织和纤维化大量增生。原位杂交研究表明，注射TGF-β可诱导注射部位真皮成纤维细胞中高水平的CTGF mRNA，表明TGF-β可在体内诱导结缔组织细胞中CTGF的表达。在对照皮肤或注射TGF-β的皮肤中的表皮细胞或对照（注射生理盐水）皮肤中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可诱导结缔组织细胞增殖和细胞外基质合成。
