Leydon Ciara, Imaizumi Mitsuyoshi, Bartlett Rebecca S, Wang Sarah F, Thibeault Susan L
Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Wisconsin - Madison, Madison, Wisconsin, United States of America.
PLoS One. 2014 Dec 16;9(12):e115389. doi: 10.1371/journal.pone.0115389. eCollection 2014.
Vocal fold epithelial cells likely play an important, yet currently poorly defined, role in healing following injury, irritation and inflammation. In the present study, we sought to identify a possible role for growth factors, epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGFβ1), in epithelial regeneration during wound healing as a necessary first step for uncovering potential signaling mechanisms of vocal fold wound repair and remodeling. Using a rat model, we created unilateral vocal fold injuries and examined the timeline for epithelial healing and regeneration during early and late stages of wound healing using immunohistochemistry (IHC). We observed time-dependent secretion of the proliferation marker, ki67, growth factors EGF and TGFβ1, as well as activation of the EGF receptor (EGFR), in regenerating epithelium during the acute phase of injury. Ki67, growth factor, and EGFR expression peaked at day 3 post-injury. Presence of cytoplasmic and intercellular EGF and TGFβ1 staining occurred up to 5 days post-injury, consistent with a role for epithelial cells in synthesizing and secreting these growth factors. To confirm that epithelial cells contributed to the cytokine secretion, we examined epithelial cell growth factor secretion in vitro using polymerase chain reaction (PCR). Cultured pig vocal fold epithelial cells expressed both EGF and TGFβ1. Our in vivo and in vitro findings indicate that epithelial cells are active participants in the wound healing process. The exact mechanisms underlying their roles in autocrine and paracrine signaling guiding wound healing await study in a controlled, in vitro environment.
声带上皮细胞可能在损伤、刺激和炎症后的愈合过程中发挥重要作用，然而目前其作用尚不清楚。在本研究中，我们试图确定生长因子、表皮生长因子（EGF）和转化生长因子-β1（TGFβ1）在伤口愈合过程中上皮再生中的可能作用，这是揭示声带伤口修复和重塑潜在信号机制的必要第一步。我们使用大鼠模型制造单侧声带损伤，并通过免疫组织化学（IHC）检查伤口愈合早期和晚期上皮愈合和再生的时间线。我们观察到在损伤急性期再生上皮中增殖标志物ki67、生长因子EGF和TGFβ1的分泌呈时间依赖性，以及表皮生长因子受体（EGFR）的激活。Ki67、生长因子和EGFR表达在损伤后第3天达到峰值。在损伤后长达5天，细胞质和细胞间均有EGF和TGFβ1染色，这与上皮细胞在合成和分泌这些生长因子中的作用一致。为了证实上皮细胞参与细胞因子分泌，我们使用聚合酶链反应（PCR）在体外检查上皮细胞生长因子分泌。培养的猪声带上皮细胞表达EGF和TGFβ1。我们的体内和体外研究结果表明，上皮细胞是伤口愈合过程中的积极参与者。它们在自分泌和旁分泌信号传导中指导伤口愈合的确切机制有待在可控的体外环境中进行研究。
