TGF-β decreases type I collagen and scarring after labioplasty

TGF-β decreases type I collagen and scarring after labioplasty
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DOI:
10.1177/154405910308200714
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发表时间:
2003-07-01
影响因子:
7.6
通讯作者:
Ohishi, M
Ohishi, M
中科院分区:
医学1区
文献类型:
--
作者:
Hosokawa, R;Nonaka, K;Ohishi, M

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唇裂是一种常见的先天性畸形,对婴儿进行阴唇成形术来修复此类缺陷通常会导致严重的疤痕形成。由于 TGF-β3 与伤口愈合有关,因此我们假设 TGF-β3 的作用是减少唇裂修复后的疤痕。在这项研究中,我们证明外源性 TGF-β3 可减少小鼠体内切开和缝合嘴唇的疤痕形成。在阴唇成形术期间,内源性 TGF-β3 表达也升高。体外实验表明,外源性TGF-β3可减少I型胶原蛋白的积累。此外,TGF-β3 抑制α-平滑肌肌动蛋白的表达,这是肌成纤维细胞的标志物。同时,TGF-β3 诱导 MMP-9 的表达和活性。我们的数据分析表明,TGF-β3 通常在唇形伤口愈合后分泌。 TGF-β3 水平升高会限制肌成纤维细胞分化,进而限制胶原蛋白合成,并通过 MMP-9 促进胶原蛋白降解,从而减少 I 型胶原蛋白沉积。综合起来,这些事件导致 TGF-β3 介导的疤痕形成减少。
Cleft lip is a common congenital malformation, and labioplasty performed on infants to repair such defects often results in severe scar formation. Since TGF-beta3 has been implicated in wound healing, we therefore hypothesized that TGF-beta3 functions to reduce scarring after cleft lip repair. In this investigation, we demonstrated that exogenous TGF-beta3 reduced scar formation in an incised and sutured mouse lip in vivo. During labioplasty, endogenous TGF-beta3 expression was also elevated. In vitro experiments showed that exogenous TGF-beta3 reduced type I collagen accumulation. Furthermore, TGF-beta3 inhibited alpha-smooth-muscle actin expression, a marker for myofibroblasts. In tandem, TGF-beta3 induced the expression and activity of MMP-9. Analysis of our data suggests that TGF-beta3 is normally secreted following labioplastic wound healing. An elevated level of TGF-beta3 reduces type I collagen deposition by restricting myofibroblast differentiation and thereby collagen synthesis, and by promoting collagen degradation by MMP-9. In combination, these events lead to TGF-beta3-mediated reduced scar formation.