Lygoe Kate A, Norman Jill T, Marshall John F, Lewis Mark P
Eastman Dental Institute, University College London, 256 Grays Inn Road, London WC1 X8LD, United Kingdom.
Wound Repair Regen. 2004 Jul-Aug;12(4):461-70. doi: 10.1111/j.1067-1927.2004.12402.x.
Transforming growth factor-beta1 is a potent mediator of the differentiation of fibroblasts into myofibroblasts, which is characterized by the appearance of the cytoskeletal protein alpha-smooth muscle actin. The aim of this study was to investigate the role of integrin extracellular matrix receptors in transforming growth factor-beta1-induced myofibroblast differentiation. We show that blockade of the alphav and/or beta1 integrins prevents the transforming growth factor-beta1-induced myofibroblast differentiation, seen by the increased expression of alpha-smooth muscle actin and enhanced collagen gel contraction in three human fibroblast cell lines (from the mouth, skin, and kidney). Further, blockade of alphav specific integrins alphavbeta5 and alphavbeta3 suppressed myofibroblast differentiation in fibroblasts from the mouth and skin; however, in the kidney cells, the prevention of differentiation was seen only with blockade of alphavbeta5 integrin but not alphavbeta3. A possible reason for this result may be different degrees of responsiveness to transforming growth factor-beta1 treatment seen from different anatomical origins of the cell lines. These data indicate a novel role for alphav integrins in the differentiation of human fibroblasts from the mouth, skin, and kidney into myofibroblasts and suggest that there is a common differentiation pathway.
转化生长因子-β1是成纤维细胞分化为肌成纤维细胞的有效介质，其特征是细胞骨架蛋白α-平滑肌肌动蛋白的出现。本研究的目的是探讨整合素细胞外基质受体在转化生长因子-β1诱导的肌成纤维细胞分化中的作用。我们发现，阻断αv和/或β1整合素可防止转化生长因子-β1诱导的肌成纤维细胞分化，这在三种人成纤维细胞系（来自口腔、皮肤和肾脏）中表现为α-平滑肌肌动蛋白表达增加和胶原凝胶收缩增强。此外，阻断αv特异性整合素αvβ5和αvβ3可抑制口腔和皮肤成纤维细胞中的肌成纤维细胞分化；然而，在肾细胞中，仅阻断αvβ5整合素而非αvβ3可观察到分化的抑制。这一结果的一个可能原因可能是不同解剖来源的细胞系对转化生长因子-β1处理的反应程度不同。这些数据表明αv整合素在人口腔、皮肤和肾脏成纤维细胞分化为肌成纤维细胞中具有新的作用，并提示存在共同的分化途径。
