Mechanical tension increases CCN2/CTGF expression and proliferation in gingival fibroblasts via a TGFβ-dependent mechanism.
Mechanical tension increases CCN2/CTGF expression and proliferation in gingival fibroblasts via a TGFβ-dependent mechanism.
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DOI：
10.1371/journal.pone.0019756
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Leask A
中科院分区：
文献类型：
--
作者：
Guo F;Carter DE;Leask A
与皮肤不同，口腔牙龈不会因组织损伤而形成疤痕。成纤维细胞是负责结缔组织修复和瘢痕形成的细胞类型，在正常和病理条件下，包括伤口愈合和纤维形成，都暴露在机械张力下。了解人类牙龈成纤维细胞如何对机械张力作出反应，不仅可能对牙龈功能产生有价值的见解，而且可能对无疤痕修复的分子基础产生有价值的见解。在组织修复和纤维形成过程中，CCN2/结缔组织生长因子在成纤维细胞中被有效诱导。我们使用Flexercell系统对牙龈成纤维细胞进行周期培养（长达72小时），结果表明菌株可诱导CCN2 mRNA和蛋白。菌株引起潜伏的tgf - β的快速激活，通过抑制blebbistatin和FAK/src，以及诱导内皮素（ET-1） mRNA和蛋白的表达而降低。菌株未诱导α-平滑肌肌动蛋白或胶原I型mrna（促进瘢痕形成的蛋白）；但诱导了一系列促增殖mrna和细胞增殖。与真皮成纤维细胞相比，牙龈成纤维细胞通过诱导成纤维mrna对TGFβ的反应能力降低；ET-1的加入挽救了这种表型。药理抑制TGFβ I型（ALK5）受体、内皮素A/B受体和FAK/src可显著降低CCN2和促增殖mrna的诱导和细胞增殖。控制TGFβ、ET-1和FAK/src活性可能有助于控制牙龈对机械应变的反应，并可能对控制牙龈增生等纤维增生性疾病有价值；控制ET-1可能有利于控制因皮肤损伤而形成的疤痕。
Unlike skin, oral gingival do not scar in response to tissue injury. Fibroblasts, the cell type responsible for connective tissue repair and scarring, are exposed to mechanical tension during normal and pathological conditions including wound healing and fibrogenesis. Understanding how human gingival fibroblasts respond to mechanical tension is likely to yield valuable insights not only into gingival function but also into the molecular basis of scarless repair. CCN2/connective tissue growth factor is potently induced in fibroblasts during tissue repair and fibrogenesis. We subjected gingival fibroblasts to cyclical strain (up to 72 hours) using the Flexercell system and showed that CCN2 mRNA and protein was induced by strain. Strain caused the rapid activation of latent TGFβ, in a fashion that was reduced by blebbistatin and FAK/src inhibition, and the induction of endothelin (ET-1) mRNA and protein expression. Strain did not cause induction of α-smooth muscle actin or collagen type I mRNAs (proteins promoting scarring); but induced a cohort of pro-proliferative mRNAs and cell proliferation. Compared to dermal fibroblasts, gingival fibroblasts showed reduced ability to respond to TGFβ by inducing fibrogenic mRNAs; addition of ET-1 rescued this phenotype. Pharmacological inhibition of the TGFβ type I (ALK5) receptor, the endothelin A/B receptors and FAK/src significantly reduced the induction of CCN2 and pro-proliferative mRNAs and cell proliferation. Controlling TGFβ, ET-1 and FAK/src activity may be useful in controlling responses to mechanical strain in the gingiva and may be of value in controlling fibroproliferative conditions such as gingival hyperplasia; controlling ET-1 may be of benefit in controlling scarring in response to injury in the skin.
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影响因子：
4.1
作者：
Leask, Andrew;Parapuram, Sunil K.;Xu Shi-wen;Abraham, D. J.
通讯作者：
Abraham, D. J.
影响因子：
4.8
作者：
Kessler, D;Dethlefsen, S;Eckes, B
通讯作者：
Eckes, B
结缔组织疾病中的纤维化：肌纤维细胞和成纤维细胞上皮细胞相互作用的作用。
影响因子：
4.9
作者：
Krieg, Thomas;Abraham, David;Lafyatis, Robert
通讯作者：
Lafyatis, Robert
影响因子：
5
作者：
Abraham, David J;Eckes, Beate;Krieg, Thomas
通讯作者：
Krieg, Thomas
影响因子：
4.1
作者：
Samarin, Jana;Cicha, Iwona;Goppelt-Struebe, Margarete
通讯作者：
Goppelt-Struebe, Margarete