Goldstein R H, Fine A, Farnsworth L J, Poliks C, Polgar P
Pulmonary Center, Boston University School of Medicine, Massachusetts.
J Biol Chem. 1990 Aug 15;265(23):13623-8.
The effect of phorbol 12-myristate 13-acetate (PMA) on collagen accumulation by human embryonic lung fibroblasts was determined. PMA (10 nM) dramatically inhibited collagen formation in cultures that were unstimulated or stimulated with transforming growth factor-beta (TGF-beta). Collagen accumulation was decreased by 50% in unstimulated cultures and by 80% in TGF-beta-treated cultures. This inhibition was associated with a marked decrease in steady-state levels for alpha 1(I) collagen mRNA and decreases in alpha 1(I) gene transcription as determined by nuclear run-off assays. The PMA-mediated decrease in alpha 1(I) collagen mRNA was not affected by the addition of cycloheximide or indomethacin. Prolonged treatment with PMA (100 nM) resulted in down-regulation of protein kinase C (PKC) activity to less than 3% of untreated cultures. When PKC activity was down-regulated, treatment with PMA did not block TGF-beta-stimulated collagen formation, and prostaglandin E2-induced inhibition of protein formation was still evident. These results suggests that PKC activity modulates the level of transcription of collagen genes and collagen accumulation in lung fibroblast cultures.
研究了佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）对人胚肺成纤维细胞胶原积累的影响。PMA（10 nM）显著抑制未受刺激或经转化生长因子-β（TGF-β）刺激的培养物中的胶原形成。在未受刺激的培养物中，胶原积累减少了50%，在经TGF-β处理的培养物中减少了80%。这种抑制作用与α1（I）型胶原mRNA的稳态水平显著降低以及通过核转录分析确定的α1（I）基因转录减少有关。添加环己酰亚胺或吲哚美辛不影响PMA介导的α1（I）型胶原mRNA的减少。用PMA（100 nM）长期处理导致蛋白激酶C（PKC）活性下调至未处理培养物的3%以下。当PKC活性下调时，用PMA处理并不阻断TGF-β刺激的胶原形成，并且前列腺素E2诱导的蛋白形成抑制仍然明显。这些结果表明，PKC活性调节肺成纤维细胞培养物中胶原基因的转录水平和胶原积累。
