BMP3 inhibits TGFβ2-mediated myofibroblast differentiation during wound healing of the embryonic cornea.
BMP3 inhibits TGFβ2-mediated myofibroblast differentiation during wound healing of the embryonic cornea.
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DOI：
10.1038/s41536-022-00232-9
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发表时间：
2022-07-25
影响因子：
7.2
通讯作者：
Lwigale, Peter Y.
中科院分区：
文献类型：
--
作者：
Spurlin, James W., III;Garis, Matthew R.;Lwigale, Peter Y.
通常，角膜的急性损伤会引发剧烈的组织重塑，导致纤维化瘢痕，从而破坏光传输并导致视力受损。关于可以减轻纤维化和促进无瘢痕角膜伤口愈合的因素知之甚少。我们先前描述了胚胎角膜损伤模型中非纤维化修复过程中短暂的肌成纤维细胞分化。在这里，我们试图阐明胚胎角膜伤口愈合过程中肌成纤维细胞分化的机制调节。我们发现α-平滑肌肌动蛋白（αSMA）阳性肌成纤维细胞是浅表的，它们的存在与伤口闭合呈负相关。在成肌纤维细胞诱导过程中，TGFβ2的表达和pSMAD 2的核定位均升高。BMP 3和BMP 7定位于角膜上皮中，并且与愈合基质中的pSMAD 1/5/8活化和肌成纤维细胞的缺乏相对应。对角膜成纤维细胞的体外分析显示，BMP 3通过促进粘连灶和αSMA纤维的分解来抑制TGFβ2诱导的肌成纤维细胞的持久性。黏着斑蛋白和pFAK的表达证实了这一点。总之，这些数据突出了在角膜伤口修复期间抑制肌成纤维细胞持久性的机制。
Often acute damage to the cornea initiates drastic tissue remodeling, resulting in fibrotic scarring that disrupts light transmission and precedes vision impairment. Very little is known about the factors that can mitigate fibrosis and promote scar-free cornea wound healing. We previously described transient myofibroblast differentiation during non-fibrotic repair in an embryonic cornea injury model. Here, we sought to elucidate the mechanistic regulation of myofibroblast differentiation during embryonic cornea wound healing. We found that alpha-smooth muscle actin (αSMA)-positive myofibroblasts are superficial and their presence inversely correlates with wound closure. Expression of TGFβ2 and nuclear localization of pSMAD2 were elevated during myofibroblast induction. BMP3 and BMP7 were localized in the corneal epithelium and corresponded with pSMAD1/5/8 activation and absence of myofibroblasts in the healing stroma. In vitro analyses with corneal fibroblasts revealed that BMP3 inhibits the persistence of TGFβ2-induced myofibroblasts by promoting disassembly of focal adhesions and αSMA fibers. This was confirmed by the expression of vinculin and pFAK. Together, these data highlight a mechanism to inhibit myofibroblast persistence during cornea wound repair.
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角膜中的TGFβ1和TGFβ2蛋白，具有和不基质纤维化：顶部上皮生长因子屏障的延迟再生以及具有基质纤维化的角膜上的上皮地下膜。
影响因子：
3.4
作者：
de Oliveira RC;Tye G;Sampaio LP;Shiju TM;DeDreu J;Menko AS;Santhiago MR;Wilson SE
通讯作者：
Wilson SE
影响因子：
2.5
作者：
Bi, Lian;Lwigale, Peter
通讯作者：
Lwigale, Peter
影响因子：
4.4
作者：
Feneck, Eleanor M.;Lewis, Philip N.;Meek, Keith M.
通讯作者：
Meek, Keith M.
成纤维细胞-肌成纤维细胞转变的机械和物理调节：从细胞机械反应到组织病理学。
影响因子：
5.7
作者：
D'Urso M;Kurniawan NA
通讯作者：
Kurniawan NA
DOI：
10.3928/1081597x-20211007-02
发表时间：
2022-01
期刊：
Journal of refractive surgery (Thorofare, N.J. : 1995)
影响因子：
--
作者：
de Oliveira RC;Sampaio LP;Shiju TM;Santhiago MR;Wilson SE
通讯作者：
Wilson SE