Department of Dentistry, University of Western Ontario, London, Ontario, Canada.
PLoS One. 2011;6(11):e27097. doi: 10.1371/journal.pone.0027097. Epub 2011 Nov 2.
Unlike skin, oral gingiva do not scar in response to injury. The basis of this difference is likely to be revealed by comparing the responses of dermal and gingival fibroblasts to fibrogenic stimuli. Previously, we showed that, compared to dermal fibroblasts, gingival fibroblasts are less responsive to the potent pro-fibrotic cytokine TGFβ, due to a reduced production of endothelin-1 (ET-1). In this report, we show that, compared to dermal fibroblasts, human gingival fibroblasts show reduced expression of pro-adhesive mRNAs and proteins including integrins α2 and α4 and focal adhesion kinase (FAK). Consistent with these observations, gingival fibroblasts are less able to adhere to and spread on both fibronectin and type I collagen. Moreover, the enhanced production of ET-1 mRNA and protein in dermal fibroblasts is reduced by the FAK/src inhibitor PP2. Given our previous observations suggesting that fibrotic fibroblasts display elevated adhesive properties, our data suggest that scarring potential may be based, at least in part, on differences in adhesive properties among fibroblasts resident in connective tissue. Controlling adhesive properties may be of benefit in controlling scarring in response to tissue injury.
与皮肤不同，口腔牙龈在受伤后不会形成瘢痕。这种差异的基础可能通过比较真皮和成牙龈成纤维细胞对纤维生成刺激的反应来揭示。此前，我们表明，与真皮成纤维细胞相比，牙龈成纤维细胞对强效促纤维化细胞因子 TGFβ的反应性较低，这是由于内皮素-1（ET-1）的产生减少。在本报告中，我们表明，与真皮成纤维细胞相比，人牙龈成纤维细胞表现出黏附性 mRNA 和蛋白质（包括整合素 α2 和 α4 和粘着斑激酶（FAK））的表达降低。与这些观察结果一致，牙龈成纤维细胞在纤维连接蛋白和 I 型胶原上的黏附和铺展能力降低。此外，真皮成纤维细胞中 ET-1 mRNA 和蛋白质的产生增加可被 FAK/src 抑制剂 PP2 降低。鉴于我们之前的观察表明纤维化成纤维细胞表现出升高的黏附特性，我们的数据表明，瘢痕形成的潜力可能至少部分基于存在于结缔组织中的成纤维细胞之间的黏附特性差异。控制黏附特性可能有益于控制组织损伤后的瘢痕形成。
