Mesenchymal stem cell-mediated suppression of hypertrophic scarring is p53 dependent in a rabbit ear model.
Mesenchymal stem cell-mediated suppression of hypertrophic scarring is p53 dependent in a rabbit ear model.
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DOI：
10.1186/scrt526
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发表时间：
2014-12-15
影响因子：
7.5
通讯作者：
Deng FM
中科院分区：
文献类型：
--
作者：
Liu YL;Liu WH;Sun J;Hou TJ;Liu YM;Liu HR;Luo YH;Zhao NN;Tang Y;Deng FM
间充质干细胞（MSC）被认为在伤口修复和组织重塑中发挥重要作用。肥厚性疤痕（HTS）是一种皮肤疾病，其特征是急性皮肤损伤后胶原蛋白沉积过多。然而，目前对于MSC与HTS之间的直接关系知之甚少。建立兔耳增生性疤痕模型。从兔股骨骨髓中分离出间充质干细胞，并通过耳动脉注射进行移植。使用冰冻切片分析、苏木精和伊红 (HE) 染色、马森三色染色和疤痕抬高指数检查肥厚性疤痕形成。通过使用 p53 shRNA 进行基因敲除来检查 p53 在 MSC 介导的抗疤痕形成作用中的作用。在这项研究中，通过耳动脉注射的MSCs植入显着抑制了兔耳肥厚性疤痕模型中的肥厚性疤痕形成，而这种抗疤痕形成功能可以通过MSCs中的p53基因敲除来消除。此外，我们发现间充质干细胞以旁分泌方式在mRNA和蛋白质水平上下调TGF-β受体I（TβRI）和α-平滑肌肌动蛋白（α-SMA）的表达，并且这种下调可以通过p53基因敲除来挽救。此外，我们的结果表明，p53 基因敲低的 MSC 通过增加一氧化氮 (NO) 的产生来促进成纤维细胞的增殖。这些结果表明MSCs通过至少两种机制以p53依赖性方式抑制HTS的形成：抑制HTS成纤维细胞向肌成纤维细胞的转化；通过抑制NO的产生来抑制成纤维细胞的增殖。
Mesenchymal stem cells (MSCs) are considered to play important roles in wound repair and tissue remodeling. Hypertrophic scar (HTS) is a cutaneous condition characterized by deposits of excessive amount of collagen after an acute skin injury. However, currently there is little knowledge about the direct relationship between MSCs and HTS. The hypertrophic scar model was established on rabbit ears. MSCs were isolated from rabbit femur bone marrow and transplanted through ear artery injection. Hypertrophic scar formation was examined using frozen-section analysis, hematoxylin and eosin (HE) staining, Masson’s trichrome staining, and scar elevation index. The role of p53 in the MSCs-mediated anti-scarring effect was examined by gene knockdown using p53 shRNA. In this study, MSCs engraftment through ear artery injection significantly inhibited the hypertrophic scarring in a rabbit ear hypertrophic scar model, while this anti-scarring function could be abrogated by p53 gene knockdown in MSCs. Additionally, we found that MSCs down-regulated the expression of TGF-β receptor I (TβRI) and alpha-smooth muscle actin (α-SMA) at both mRNA and protein levels in a paracrine manner, and this down-regulation was rescued by p53 gene knockdown. Moreover, our results showed that MSCs with p53 gene knockdown promoted the proliferation of fibroblasts through increasing nitric oxide (NO) production. These results suggest that MSCs inhibit the formation of HTS in a p53 dependent manner through at least two mechanisms: inhibition of the transformation of HTS fibroblast to myofibroblast; and inhibition of the proliferation of fibroblasts through inhibition of NO production.
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