Regulation of epithelial differentiation and proliferation by the stroma: a role for the retinoblastoma protein.
Regulation of epithelial differentiation and proliferation by the stroma: a role for the retinoblastoma protein.
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DOI：
10.1038/jid.2012.201
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发表时间：
2012-12
影响因子：
6.5
通讯作者：
McCance, Dennis J.
中科院分区：
文献类型：
--
作者：
Pickard, Adam;Cichon, Ann-Christin;Menges, Craig;Patel, Daksha;McCance, Dennis J.
上皮细胞和基质细胞之间的信号传导对于上皮细胞的生长、分化和修复至关重要。虽然视网膜母细胞瘤蛋白是已知的调节角质形成细胞的生长，在一个细胞自主的方式，在这里，我们描述了Rb在基质室的功能。我们发现，Rb耗竭成纤维细胞导致分化的抑制和上皮细胞的增殖增强。条件培养基的分析确定，角质形成细胞生长因子（KGF）水平升高Rb耗竭后。这些发现也观察到与器官型共培养。角质形成细胞与KGF的治疗抑制分化和增强角质形成细胞增殖，而减少Rb耗竭成纤维细胞中的KGF水平能够恢复分化标志物的表达。我们的研究结果表明，真皮成纤维细胞在调节角质形成细胞的分化和增殖中起着至关重要的作用，我们证明了基质Rb在这种串扰中的作用。
Signalling between the epithelium and stromal cells is crucial for growth, differentiation and repair of the epithelium. While the retinoblastoma protein is known to regulate the growth of keratinocytes, in a cell-autonomous fashion, here we describe a function of Rb in the stromal compartment. We find that Rb depletion in fibroblasts leads to inhibition of differentiation and enhanced proliferation of the epithelium. Analysis of conditioned medium identified that keratinocyte growth factor (KGF) levels were elevated following Rb depletion. These findings were also observed with organotypic co-cultures. Treatment of keratinocytes with KGF inhibited differentiation and enhanced keratinocyte proliferation, whilst reduction of KGF levels in Rb-depleted fibroblasts was able to restore expression of differentiation markers. Our findings suggest a crucial role for dermal fibroblasts in regulating the differentiation and proliferation of keratinocytes, and we demonstrate a role for stromal Rb in this cross-talk.
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