Reduced Decorin, Fibromodulin, and Transforming Growth Factor-β3 in Deep Dermis Leads to Hypertrophic Scarring
Reduced Decorin, Fibromodulin, and Transforming Growth Factor-β3 in Deep Dermis Leads to Hypertrophic Scarring
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DOI：
10.1097/bcr.0b013e3182335980
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发表时间：
2012-03-01
影响因子：
1.4
通讯作者：
Tredget, Edward E.
中科院分区：
文献类型：
--
作者：
Honardoust, Dariush;Varkey, Mathew;Tredget, Edward E.
肥厚性瘢痕（HTS）发生在涉及深层真皮的损伤之后，而皮肤的浅表伤口（SW）愈合时具有最小的瘢痕或没有瘢痕。转化生长因子（TGF）-β 1和富含亮氨酸的小蛋白聚糖（SLRP）水平与成纤维细胞亚型和功能可能会影响HTS的发展。本研究的目的是表征调节伤口愈合的因子的表达和定位，包括SLRP、TGF-β 1和TGF-β 3在实验性人类SW和深层伤口（DW）瘢痕模型中的表达和定位，所述模型包括来自正常真皮的浅表层和深层的成纤维细胞。产生6-cm水平皮肤划痕实验伤口，其由逐渐加深的伤口组成，所述伤口在一端是浅的（0-0.75 mm深）并且在另一端是深的（0.75-3 mm深），位于成年男性的大腿前部。采用免疫荧光染色、免疫印迹、逆转录聚合酶链反应和流式细胞术分析SW瘢痕和DW瘢痕以及正常真皮浅层（L1）和深层（L5）成纤维细胞的细胞和分子差异。比较SW和L1成纤维细胞，核心蛋白聚糖、纤维调节蛋白和TGF-β 3的表达显著低于DW和L5成纤维细胞;然而，TGF-β 1在更深的真皮伤口中更高。与L1成纤维细胞相比，L5成纤维细胞具有较低的Thy-1免疫反应性和显著较高的TGF-β受体II型表达。皮肤深层真皮基质中抗纤维化分子的减少和相关成纤维细胞的独特特征（包括对TGF-β 1刺激的敏感性增加）有助于涉及深层真皮的损伤后HTS的发展。（J Burn Care Res 2012;33：218-227）
Hypertrophic scar (HTS) occurs after injuries involving the deep dermis, while superficial wounds (SWs) to the skin heal with minimal or no scarring. The levels of transforming growth factor (TGF)-beta 1 and small leucine-rich proteoglycans (SLRPs) with fibroblast subtype and function may influence the development of HTS. The aim of this study was to characterize the expression and localization of factors that regulate wound healing including SLRPs, TGF-beta 1, and TGF-beta 3 in an experimental human SW and deep wound (DW) scar model including fibroblasts from superficial and deep layers of normal dermis. A 6-cm horizontal dermal scratch experimental wound was created, which consisted of progressively deeper wounds that were superficial at one end (0-0.75 mm deep) and deep (0.75-3 mm deep) at the other end, located on the anterior thigh of an adult male. Immunofluorescence staining, immunoblotting, reverse transcription polymerase chain reaction, and flow cytometry were performed to analyze the cellular and molecular differences between the SW scar and DW scar as well as fibroblasts isolated from superficial layer (L1) and deep layer (L5) of normal dermis. Comparing SWs and L1 fibroblasts, the expression of decorin, fibromodulin, and TGF-beta 3 was considerably lower than in DWs and L5 fibroblasts; however, TGF-beta 1 was higher in the deeper dermal wounds. When compared with L1 fibroblasts, L5 fibroblasts had lower Thy-1 immunoreactivity and significantly higher expression of TGF-beta receptor type II. Decreased antifibrotic molecules in matrix of deep dermis of the skin and the unique features of the associated fibroblasts including an increased sensitivity to TGF-beta 1 stimulation contribute to the development of HTS after injuries involving the deep dermis. (J Burn Care Res 2012;33:218-227)