The cxc chemokine cCAF stimulates differentiation of fibroblasts into myofibroblasts and accelerates wound closure.
The cxc chemokine cCAF stimulates differentiation of fibroblasts into myofibroblasts and accelerates wound closure.
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DOI：
10.1083/jcb.200103062
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发表时间：
2002-01-07
期刊：
影响因子：
--
通讯作者：
Martins-Green M
中科院分区：
文献类型：
--
作者：
Feugate JE;Li Q;Wong L;Martins-Green M
趋化因子是一种小的细胞因子，主要以其在炎症中的作用而闻名。然而，最近，它们被认为参与了伤口肉芽组织的发育过程，但对它们在这一过程中的作用知之甚少。成纤维细胞在这一阶段的愈合中起着关键作用：一些成纤维细胞分化为肌成纤维细胞，即在伤口闭合和收缩中起重要作用的α-平滑肌肌动蛋白产生细胞。在这里，我们展示了CXC趋化因子和血管生成因子(CCAF)刺激成纤维细胞产生高水平的α-SMA，并比正常成纤维细胞更有效地收缩胶原胶，这两个特性都是肌成纤维细胞的特征。特异性抑制α-SMA的表达可消除CCAF诱导的收缩。此外，将CCAF应用于体内创面，增加了肉芽组织中存在的肌成纤维细胞的数量，并加速了创面的闭合和收缩。我们还表明，在培养和体内，这些作用可以通过含有CCAF蛋白NH2端15个氨基酸的多肽来实现，抑制α-SMA的表达也会导致抑制N-肽诱导的胶原凝胶收缩。我们认为，在修复组织的形成过程中，趋化因子是使成纤维细胞分化为肌成纤维细胞的主要因素。由于肌成纤维细胞在许多病理条件下都是重要的，而且趋化因子及其受体可受药物操纵，趋化因子刺激肌成纤维细胞分化可能对体内这些细胞的功能调节有一定的意义。
Chemokines are small cytokines primarily known for their roles in inflammation. More recently, however, they have been implicated in processes involved in development of the granulation tissue of wounds, but little is known about their functions during this process. Fibroblasts play key roles in this phase of healing: some fibroblasts differentiate into myofibroblasts, α-smooth muscle actin (SMA)-producing cells that are important in wound closure and contraction. Here we show that the CXC chemokine chicken chemotactic and angiogenic factor (cCAF) stimulates fibroblasts to produce high levels of α-SMA and to contract collagen gels more effectively than do normal fibroblasts, both characteristic properties of myofibroblasts. Specific inhibition of α-SMA expression resulted in abrogation of cCAF-induced contraction. Furthermore, application of cCAF to wounds in vivo increases the number of myofibroblasts present in the granulation tissue and accelerates wound closure and contraction. We also show that these effects in culture and in vivo can be achieved by a peptide containing the NH2-terminal 15 amino acids of the cCAF protein and that inhibition of α-SMA expression also results in inhibition of N-peptide–induced collagen gel contraction. We propose that chemokines are major contributors for the differentiation of fibroblasts into myofibroblasts during formation of the repair tissue. Because myofibroblasts are important in many pathological conditions, and because chemokines and their receptors are amenable to pharmacological manipulations, chemokine stimulation of myofibroblast differentiation may have implications for modulation of functions of these cells in vivo.
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DOI：
10.1083/jcb.107.6.2757
发表时间：
1988-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mackie EJ;Halfter W;Liverani D
通讯作者：
Liverani D
DOI：
10.1083/jcb.127.4.1121
发表时间：
1994-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gupta SK;Singh JP
通讯作者：
Singh JP
影响因子：
14
作者：
Khouw, IMSL;van Wachem, PB;van Luyn, MJA
通讯作者：
van Luyn, MJA
影响因子：
3.9
作者：
Kadono, T;Kikuchi, K;Tamaki, K
通讯作者：
Tamaki, K
影响因子：
2.4
作者：
Lanning, DA;Diegelmann, RF;Haynes, JH
通讯作者：
Haynes, JH