Regulation of transforming growth factor-β1 expression by granulocyte macrophage-colony-stimulating factor in leiomyoma and myometrial smooth muscle cells
Regulation of transforming growth factor-β1 expression by granulocyte macrophage-colony-stimulating factor in leiomyoma and myometrial smooth muscle cells
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DOI：
10.1210/jc.84.11.4138
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发表时间：
1999-11-01
影响因子：
5.8
通讯作者：
Ma, CF
中科院分区：
文献类型：
--
作者：
Chegini, N;Tang, XM;Ma, CF
人肌层和平滑肌瘤表达粒细胞巨噬细胞集落刺激因子（GM-CSF）、转化生长因子- β (TGF β)及其受体。TGF β的过表达以及有限程度上的GM-CSF与包括肌瘤在内的全身组织纤维化有关。本研究的目的是确定GM-CSF对平滑肌瘤和子宫肌平滑肌细胞（LSMC和MSMC）的作用，并探讨GM-CSF的作用是否通过诱导TGF β 1表达介导。通过竞争性定量RT-PCR和酶联免疫吸附实验，我们发现LSMC表达的GM-CSF信使核糖核酸（mRNA; 0.6 +/- 0.1 × 10(3)份mRNA/ μ g总RNA）和蛋白质（0.75 +/- 0.2 ng/mL）显著高于MSMC （0.5 +/- 0.1 × 10(2)份mRNA和0.45 +/- 0.07 ng/mL蛋白）；P < 0.05)。此外，LSMC表达TGF β 1 mRNA （1.6 +/- 0.3 × 10(4) copies / μ g总RNA）明显高于MSMC (2.4 +/- 0.4 × 103 copies / μ g总RNA)，合成和分泌更多TGF β 1蛋白（1.7 +/- 0.2 vs. 0.5 +/- 0.02 ng/mL）；而MSMC细胞相关TGF β 1含量（56.2 +/- 1.2 ng/mL）高于LSMC （35.2 +/- 1.2 ng/mL, P < 0.05）。我们发现GM-CSF （0.01-100 ng/mL）对LSMC有有限的有丝分裂活性，但对MSMC没有，这是通过[H-3]胸腺嘧啶掺入率和细胞增殖试验确定的。而在1 ng/mL时，GM-CSF的自身产量、TGF β 1 mRNA的表达、两种细胞中细胞相关TGF β 1蛋白的含量以及TGF β 1释放到LSMC培养条件培养基中均增加（P < 0.05）。TGF β 1也增加了自身mRNA和蛋白的表达，但在两种细胞类型中对细胞相关TGF β 1均无影响（P < 0.05）。LSMC和MSMC与GM-CSF和TGF β 1共处理，在两种细胞中诱导的变化与GM-CSF产生的变化相似。总之，我们的数据表明GM-CSF不是MSMC和LSMC的丝裂原，但它调节其自身的表达以及这些细胞对TGF β 1的表达，这种调节相互作用可能解释了GM-CSF诱导的平滑肌瘤中发生的组织纤维化。
Human myometrium and leiomyomas express granulocyte macrophage-colony-stimulating factor (GM-CSF), transforming growth factor-beta (TGF beta), and their receptors. Overexpression of TGF beta and, to a limited extent, GM-CSF has been associated with tissue fibrosis throughout the body, including leiomyomas. The objective of the present study was to determine the action of GM-CSF on leiomyoma and myometrial smooth muscle cells (LSMC and MSMC) and examine whether the action of GM-CSF is mediated through the induction of TGF beta 1 expression. Using competitive quantitative RT-PCR and enzyme-linked immunosorbent assay, we found that LSMC express significantly higher GM-CSF messenger ribonucleic acid (mRNA; 0.6 +/- 0.1 x 10(3) copies of mRNA/mu g total RNA) and protein (0.75 +/- 0.2 ng/mL than MSMC (0.5 +/- 0.1 x 10(2) copies of mRNA and 0.45 +/- 0.07 ng/mL protein; P < 0.05). In addition, LSMC expressed significantly higher TGF beta 1 mRNA (1.6 +/- 0.3 x 10(4) copies of mRNA/mu g total RNA) than MSMC (2.4 +/- 0.4 x 103 copies) and synthesized and secreted more TGF beta 1 protein (1.7 +/- 0.2 vs. 0.5 +/- 0.02 ng/mL); whereas MSMC contained more cell-associated TGF beta 1 (56.2 +/- 1.2 ng/mL) than LSMC (35.2 +/- 1.2 ng/mL; P < 0.05). We found that GM-CSF (0.01-100 ng/mL) has limited mitogenic activity for LSMC but not for MSMC determined by the rate of [H-3]thymidine incorporation and cell proliferation assay. However, GM-CSF at 1 ng/mL increased its own production, the expression of TGF beta 1 mRNA, the cell-associated TGF beta 1 protein content in both cell types, and TGF beta 1 released into the culture-conditioned medium of LSMC (P < 0.05). TGF beta 1 also increased its own mRNA and protein expression, but had no effect on cell-associated TGF beta 1 in both cell types (P < 0.05). Cotreatment of LSMC and MSMC with GM-CSF and TGF beta 1 induced changes similar to those produced by GM-CSF in both cells. In conclusion, our data suggest that GM-CSF is not a mitogen for MSMC and LSMC, but it regulates its own expression and the expression of TGF beta 1 by these cells, a regulatory interaction that may account for the GM-CSF-induced tissue fibrosis that occurs in leiomyomas.