BMP signaling induces cell-type-specific changes in gene expression programs of human keratinocytes and fibroblasts.

BMP signaling induces cell-type-specific changes in gene expression programs of human keratinocytes and fibroblasts.
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DOI:
10.1038/jid.2009.259
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发表时间:
2010-02
期刊:
The Journal of investigative dermatology
影响因子:
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通讯作者:
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中科院分区:
其他
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BMP 信号在皮肤发育和体内平衡中发挥着至关重要的作用,而其参与调节角质形成细胞和成纤维细胞基因表达程序的分子机制仍然很大程度上未知。我们在这里证明了几种 BMP 配体、所有 BMP 受体和 BMP 相关的 Smad1/5/8 在人原代表皮角质形成细胞和真皮成纤维细胞中表达。 BMP-4 对两种细胞类型的处理都会导致 BMP-Smad 通路的激活,但不会激活 BMP-MAPK 通路。整体微阵列分析显示,BMP-4 治疗可诱导角质形成细胞和成纤维细胞的基因表达程序发生明显的细胞类型特异性变化,这比之前描述的 BMP 对细胞增殖/分化的影响要复杂得多。此外,我们的数据表明,角质形成细胞和成纤维细胞中 BMP-4 对细胞粘附、细胞外基质重塑、运动、代谢、信号传导和转录的潜在调节可能是通过不同的细胞类型特异性分子组来实现的。因此,这些数据为描述 BMP 通路对皮肤不同细胞群的不同作用的机制提供了重要基础,并将有助于进一步建立调节健康和疾病中皮肤稳态的分子信号网络。
BMP signalling plays a crucial role in skin development and homeostasis, whereas molecular mechanisms underlying its involvement in regulating gene expression programs in keratinocytes and fibroblasts remain largely unknown. We demonstrate here that several BMP ligands, all BMP receptors and BMP-associated Smad1/5/8 are expressed in human primary epidermal keratinocytes and dermal fibroblasts. Treatment of both cell types by BMP-4 resulted in the activation of the BMP-Smad, but not BMP-MAPK pathways. Global microarray analysis revealed that BMP-4 treatment induces distinct and cell-type specific changes in gene expression programmes in keratinocytes and fibroblasts, which are far more complex versus the effects of BMPs on cell proliferation/differentiation described previously. Furthermore, our data suggest that potential modulation of cell adhesion, extracellular matrix remodelling, motility, metabolism, signalling and transcription by BMP-4 in keratinocytes and fibroblasts is likely to be achieved by the distinct and cell type-specific sets of molecules. Thus, these data provide an important basis for delineating mechanisms that underlie the distinct effects of the BMP pathway on different cell populations in the skin and will be helpful in further establishing molecular signalling networks regulating skin homeostasis in health and disease.
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