Diaz A, Jiménez S A
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Int J Biochem Cell Biol. 1997 Jan;29(1):251-60. doi: 10.1016/s1357-2725(96)00112-4.
Interferon-gamma (IFN-gamma) regulates the expression of collagen and fibronectin genes by molecular mechanisms not completely understood. We investigated the effects of IFN-gamma on the expression of the genes encoding alpha 1 (I) procollagen (COL1A1), alpha 1 (III) procollagen (COL3A1), and fibronectin (FN) in cultured normal human lung fibroblasts. Labeled newly synthesized proteins were analysed by electrophoresis, mRNA levels and stability by Northern hybridizations, and transcription rates by in vitro assays. IFN-gamma caused a reduction in the production of alpha 1 (I) and alpha 1 (III) procollagens and of fibronectin. The reduction in the production of procollagen chains was shown to result from a combination of IFN-gamma-induced inhibition of the transcription rates of the COL1A1 and COL3A1 genes and destabilization of the corresponding transcripts. IFN-gamma increased the transcription rate of FN, but also decreased the stability of the corresponding transcripts. The net results indicate that the regulation of the expression of extracellular matrix genes by IFN-gamma is a complex process that involves changes in gene transcription rates, alterations in mRNAs stability, and possibly, modulation of the rates of translation.
γ干扰素（IFN-γ）通过尚未完全明确的分子机制调节胶原蛋白和纤连蛋白基因的表达。我们研究了IFN-γ对培养的正常人肺成纤维细胞中编码α1（I）前胶原（COL1A1）、α1（III）前胶原（COL3A1）和纤连蛋白（FN）的基因表达的影响。通过电泳分析标记的新合成蛋白质，通过Northern杂交分析mRNA水平和稳定性，通过体外试验分析转录率。IFN-γ导致α1（I）和α1（III）前胶原以及纤连蛋白的产生减少。前胶原链产生的减少表明是IFN-γ诱导的COL1A1和COL3A1基因转录率抑制以及相应转录本不稳定共同作用的结果。IFN-γ增加了FN的转录率，但也降低了相应转录本的稳定性。最终结果表明，IFN-γ对细胞外基质基因表达的调节是一个复杂的过程，涉及基因转录率的变化、mRNA稳定性的改变，以及可能的翻译速率调节。
