TGF-β3 modulates the inflammatory environment and reduces scar formation following vocal fold mucosal injury in rats.
TGF-β3 modulates the inflammatory environment and reduces scar formation following vocal fold mucosal injury in rats.
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DOI：
10.1242/dmm.013326
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发表时间：
2014-01
影响因子：
4.3
通讯作者：
Welham NV
中科院分区：
文献类型：
--
作者：
Chang Z;Kishimoto Y;Hasan A;Welham NV
据报道，转化生长因子（TGF）-β1和TGF-β3对伤口愈合有不同的作用，甚至可能导致瘢痕形成的组织特异性差异。瘢痕形成在声带粘膜（VFM）中特别有害，其中天然细胞外基质的破坏导致不可修复的生物力学变化和语音障碍。在这里，在一系列体外和体内实验中，我们确定了TGF-β1和TGF-β3转录和免疫定位在幼稚和受损大鼠VFM中的各种细胞亚群中的差异，与口腔粘膜（经历快速愈合，瘢痕最小）和皮肤（通常愈合瘢痕）相比。与TGF-β1和TGF-β2处理相比，TGF-β3处理培养的人声带成纤维细胞导致促纤维化基因转录、细胞外基质合成和成纤维细胞-肌成纤维细胞分化的诱导作用较弱。最后，在急性损伤阶段向大鼠VFM递送外源性TGF-β3调节了早期炎症环境并减少了最终的瘢痕形成。这些实验表明，TGF-β同种型在VFM维持和修复中具有不同的作用，并且TGF-β3重定向伤口愈合以改善体内VFM瘢痕结果。
Transforming growth factor (TGF)-β1 and TGF-β3 have been reported to exert differential effects on wound healing, and possibly even account for tissue-specific differences in scar formation. Scarring is particularly detrimental in the vocal fold mucosa (VFM), where destruction of the native extracellular matrix causes irreparable biomechanical changes and voice impairment. Here, in a series of in vitro and in vivo experiments, we identified differences in TGF-β1 and TGF-β3 transcription and immunolocalization to various cell subpopulations in naïve and injured rat VFM, compared with oral mucosa (which undergoes rapid healing with minimal scar) and skin (which typically heals with scar). Treatment of cultured human vocal fold fibroblasts with TGF-β3 resulted in less potent induction of profibrotic gene transcription, extracellular matrix synthesis and fibroblast-myofibroblast differentiation, compared with treatment with TGF-β1 and TGF-β2. Finally, delivery of exogenous TGF-β3 to rat VFM during the acute injury phase modulated the early inflammatory environment and reduced eventual scar formation. These experiments show that the TGF-β isoforms have distinct roles in VFM maintenance and repair, and that TGF-β3 redirects wound healing to improve VFM scar outcomes in vivo.
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