Bleomycin increases steady-state levels of type I collagen, fibronectin and decorin mRNAs in human skin fibroblasts

Bleomycin increases steady-state levels of type I collagen, fibronectin and decorin mRNAs in human skin fibroblasts
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博来霉素可增加人皮肤成纤维细胞中 I 型胶原蛋白、纤连蛋白和核心蛋白聚糖 mRNA 的稳态水平

DOI:
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发表时间:
2000
影响因子:
3
通讯作者:
T. Krieg
T. Krieg
中科院分区:
医学3区
文献类型:
--
作者:
Toshiyuki Yamamoto;B. Eckes;T. Krieg

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摘要博莱霉素是一种能诱导组织纤维化的药物。在本研究中,博莱霉素对细胞外基质编码的基因表达的影响1(I)胶原,纤维连接蛋白和核心蛋白聚糖在体外人真皮成纤维细胞进行了测定。北方印迹分析显示,博莱霉素在1 nM和1 μ M之间剂量依赖性地上调·1(I)胶原、纤连蛋白和核心蛋白聚糖基因表达。在正常皮肤成纤维细胞单层中,100 nM的博来霉素上调α1(I)胶原、纤连蛋白和核心蛋白聚糖mRNA的表达,在刺激后6 h达到峰值。博来霉素增强正常皮肤和硬皮病成纤维细胞中编码这些细胞外基质蛋白的mRNA表达。博莱霉素和干扰素-γ(1000 U/ml)(一种代表性的抗纤维化细胞因子)的伴随刺激降低了·1(I)胶原mRNA的表达。博莱霉素还可协同上调正常皮肤成纤维细胞中转化生长因子-β(TGF-β)和结缔组织生长因子(CTGF)的mRNA表达。我们的研究结果表明,博来霉素调节真皮成纤维细胞细胞外基质蛋白的基因表达,这种作用可能是由TGF-β和CTGF介导的。
Abstract Bleomycin is a drug capable of inducing tissue fibrosis. In this study, the effects of bleomycin on gene expression of extracellular matrix encoding ·1(I) collagen, fibronectin and decorin were determined in vitro in human dermal fibroblasts. Northern blot analysis showed that bleomycin upregulated ·1(I) collagen, fibronectin and decorin gene expression dose-dependently between 1 n M and 1 μ M . Bleomycin at 100 n M upregulated α1(I) collagen, fibronectin and decorin mRNA expression with a peak at 6 h following stimulation in normal skin fibroblast monolayers. Bleomycin enhanced mRNA expression encoding these extracellular matrix proteins in both normal dermal and scleroderma fibroblasts. Concomitant stimulation with bleomycin and interferon-γ (1000 U/ml), a representative antifibrotic cytokine, decreased ·1(I) collagen mRNA expression. Bleomycin also mildly upregulated mRNA expression of transforming growth factor-‚ (TGF-‚) and connective tissue growth factor (CTGF) coordinately in normal skin fibroblasts. Our results indicate that bleomycin modulates gene expression of extracellular matrix proteins in dermal fibroblasts, and this effect may be mediated by TGF-‚ and CTGF.
博来霉素选择性提高急性肺损伤后原胶原和纤连蛋白的 mRNA 水平。
DOI: 10.1016/0006-291x(85)91315-4
发表时间: 1985
影响因子: 3.1
作者:
Kelley,J;Chrin,L;Shull,S;Rowe,DW;Cutroneo,KR
通讯作者: Cutroneo,KR
DOI: --
发表时间: 1986-03
期刊: The Journal of biological chemistry
影响因子: --
作者:
R. Ignotz;J. Massagué
通讯作者: R. Ignotz;J. Massagué
DOI: 10.1111/1523-1747.ep12363389
发表时间: 1996-09-01
影响因子: 6.5
作者:
Frazier, K;Williams, S;Grotendorst, GR
通讯作者: Grotendorst, GR
DOI: 10.1172/jci112163
发表时间: 1985-01-01
影响因子: 15.9
作者:
RAGHOW, R;LURIE, S;KANG, AH
通讯作者: KANG, AH
DOI: 10.1136/thx.48.10.959
发表时间: 1993-10-01
期刊: THORAX
影响因子: 10
作者:
GIRI, SN;HYDE, DM;HOLLINGER, MA
通讯作者: HOLLINGER, MA