BMP-7 attenuates TGF-β1-induced fibroblast-like differentiation of rat dermal papilla cells
BMP-7 attenuates TGF-β1-induced fibroblast-like differentiation of rat dermal papilla cells
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DOI：
10.1111/wrr.12015
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发表时间：
2013-03-01
影响因子：
2.9
通讯作者：
Xie, Ju-Lin
中科院分区：
文献类型：
--
作者：
Bin, Shu;Li, Hou-Dong;Xie, Ju-Lin
毛乳头细胞（DPC）在创伤愈合过程中表现出表型可塑性。DPC的多能性是公认的，但调节这些细胞分化为成纤维细胞的信号传导途径知之甚少。初步实验表明，转化生长因子β 1（TGF-β 1）可以诱导DPC分化为成纤维细胞样细胞，这表明DPC可能是伤口愈合成纤维细胞的来源。骨形态发生蛋白-7（BMP-7）是TGF-β超家族的成员，可通过抵消TGF-β 1介导的促纤维化作用来预防和逆转纤维化。为了确定BMP-7是否减弱TGF-β 1诱导的DPC向成纤维细胞的分化，我们建立了DPC分化的体外系统，并记录了区分DPC和成纤维细胞的基因表达模式。免疫细胞化学、流式细胞术、实时定量逆转录聚合酶链反应和Western印迹分析证实，TGF-β 1处理的DPC中成纤维细胞样细胞的比例显著增加。BMP-7和TGF-β 1给药显著降低了成纤维细胞样分化，表明TGF-β 1诱导的分化受到抑制。拮抗性BMP-7和TGF-β 1激活的信号传导途径可用于促进伤口愈合或抑制增生性瘢痕形成。
Dermal papilla cells (DPCs) show phenotypic plasticity during wound healing. The multipotency of DPCs is well recognized, but the signaling pathways that regulate the differentiation of these cells into fibroblasts are poorly understood. A preliminary experiment showed that transforming growth factor beta1 (TGF-beta 1) can induce DPCs to differentiate into fibroblast-like cells, which suggests that DPCs may be a source of wound-healing fibroblasts. Bone morphogenetic protein-7 (BMP-7), a member of the TGF-beta superfamily, can prevent and reverse fibrosis by counteracting the TGF-beta 1-mediated profibrotic effect. To determine whether BMP-7 attenuates the TGF-beta 1-induced differentiation of DPCs into fibroblasts, we established an in vitro system for DPC differentiation and recorded the gene expression patterns that distinguished DPCs from fibroblasts. The proportion of fibroblast-like cells was significantly enhanced in DPCs treated with TGF-beta 1, as evidenced by immunocytochemistry, flow cytometry, quantitative real-time reverse transcriptase polymerase chain reaction, and Western blot analysis. BMP-7 and TGF-beta 1 administration substantially decreased fibroblast-like differentiation, indicating inhibition of TGF-beta 1-induced differentiation. The antagonistic BMP-7- and TGF-beta 1-activated signaling pathways can be used to promote wound healing or suppress hypertrophic scarring.