Basic fibroblast growth factor promotes apoptosis and suppresses granulation tissue formation in acute incisional wounds
Basic fibroblast growth factor promotes apoptosis and suppresses granulation tissue formation in acute incisional wounds
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DOI：
10.1002/path.1574
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发表时间：
2004-06-01
影响因子：
7.3
通讯作者：
Ishii, T
中科院分区：
文献类型：
--
作者：
Akasaka, Y;Ono, I;Ishii, T
在肉芽组织修复过程中，细胞因子被认为在细胞丢失和细胞凋亡中起重要作用。为探讨碱性成纤维细胞生长因子(BFGF)对创面细胞凋亡的作用，本研究观察了大鼠皮肤切开创面应用碱性成纤维细胞生长因子(BFGF)后肉芽组织形成程度与细胞凋亡水平的关系。创面组织宽度的组织学评估显示，1MUG-bFGF处理组的肉芽组织程度在第7天时增加，但随后在第14天和第28天时减弱。TUNEL指数从1d开始迅速升高，7d达到高峰，1mug-bFGF组在4d、7d和14d高于对照组。随着TUNEL指数在前14天的显著增加，1-MUG-bFGF处理的创面中Vimentin和CD3阳性细胞的数量在14天时已经减少。根据这些结果，推测碱性成纤维细胞生长因子对创面肉芽组织形成的抑制主要是由于肉芽组织细胞早期和持续的凋亡增加所致。碱性成纤维细胞生长因子β1和碱性成纤维细胞生长因子在第4天和第7天的创面均有表达，提示碱性成纤维细胞生长因子可诱导成纤维细胞的凋亡。出乎意料的是，在第28天，碱性成纤维细胞生长因子处理的伤口的撕裂强度并没有降低。这些结果表明，bFGF对伤口的细胞凋亡调节可能有效地促进肉芽组织的形成，促进无瘢痕的修复过程。版权所有(C)2004年大不列颠和爱尔兰病理学会。作者：John Wiley Sons，Ltd.
Cytokines are thought to play an important role in cellular loss and apoptosis during the repair of granulation tissue. In order to investigate the role of apoptosis following the administration of basic fibroblast growth factor (bFGF) to a wound, the present study examined the relationship between the degree of granulation tissue formation and the level of apoptosis in rat skin incisional wounds, following treatment with an intradermal injection of bFGF (0.1 mug and 1 mug per em of wound). Histological assessment of the width of the wound tissue showed that the degree of granulation tissue in the 1 mug-bFGF-treated group had increased by day 7, but then subsequently diminished by days 14 and 28. The TUNEL index increased rapidly from day 1, peaking on day 7, with the index being higher in the 1 mug-bFGF-treated group on days 4, 7, and 14, when compared with a control group. In parallel with a marked increase in the TUNEL index over the first 14 days, the number of cells positive for vimentin and CD3 in the 1 mug-bFGF-treated wounds had decreased by day 14. The number of PCNA-positive cells, an indicator of cell proliferation, peaked on day 4 in the bFGF-treated wounds and then declined rapidly. On the basis of these results, it is suggested that the suppression of granulation tissue formation in bFGF-treated wounds is mainly due to an early and persistent increase in apoptosis in the granulation tissue cells. The expression of both transforming growth factor (TGF)-beta1 and bFGF was also elevated in the bFGF-treated wounds on days 4 and 7, suggesting that fibroblast apoptosis was induced by bFGF treatment. Unexpectedly, on day 28, the wound breaking strength was not reduced in the bFGF-treated wounds. These results indicate that apoptosis regulation following bFGF administration to an incisional wound may lead effectively to granulation tissue formation and promote a scar-less repair process. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.