Lazard D S, Moore A, Hupertan V, Martin C, Escabasse V, Dreyfus P, Burgel P-R, Amselem S, Escudier E, Coste A
INSERM U955 and Université Paris 12, Créteil, Hôpital Armand-Trousseau, Paris, France.
Allergy. 2009 Aug;64(8):1136-43. doi: 10.1111/j.1398-9995.2009.02003.x. Epub 2009 Feb 24.
Epithelial damage and modifications of cell differentiation are frequent in airway diseases with chronic inflammation, in which transforming growth factor-beta1 (TGF-beta1) plays an important role. The aim of this study was to evaluate the differentiation of human nasal epithelial cells (HNEC) after wound healing and the potential effects of TGF-beta1.
Basal, mucus, and ciliated cells were characterized by cytokeratin-14, MUC5AC, and betaIV tubulin immunodetection, respectively. Their expression was evaluated in situ in nasal polyps and in an in vitro model of wound healing in primary cultures of HNEC after wound closure, under basal conditions and after TGF-beta1 supplementation. Using RT-PCR, the effects of TGF-beta1 on MUC5AC and DNAI1 genes, specifically transcribed in mucus and ciliated cells, were evaluated.
In situ, high TGF-beta1 expression was associated with low MUC5AC and betaIV tubulin expression. In vitro, under basal conditions, MUC5AC expression remained stable, cytokeratin-14 expression was strong and decreased with time, while betaIV tubulin expression increased. Transforming growth factor-beta1 supplementation downregulated MUC5AC and betaIV tubulin expression as well as MUC5AC and DNAI1 transcripts.
After a wound, differentiation into mucus and ciliated cells was possible and partially inhibited in vitro by TGF-beta1, a cytokine that may be involved in epithelial remodeling observed in chronic airway diseases.
上皮损伤和细胞分化改变在伴有慢性炎症的气道疾病中很常见,其中转化生长因子-β1(TGF-β1)发挥着重要作用。本研究的目的是评估伤口愈合后人鼻上皮细胞(HNEC)的分化情况以及TGF-β1的潜在影响。
分别通过细胞角蛋白-14、MUC5AC和βIV微管蛋白免疫检测来鉴定基底细胞、黏液细胞和纤毛细胞。在鼻息肉原位以及伤口闭合后HNEC原代培养物伤口愈合的体外模型中,在基础条件下和补充TGF-β1后,评估它们的表达。使用逆转录聚合酶链反应(RT-PCR),评估TGF-β1对特异性在黏液细胞和纤毛细胞中转录的MUC5AC和DNAI1基因的影响。
在原位,高TGF-β1表达与低MUC5AC和βIV微管蛋白表达相关。在体外,在基础条件下,MUC5AC表达保持稳定,细胞角蛋白-14表达强烈且随时间下降,而βIV微管蛋白表达增加。补充TGF-β1下调了MUC5AC和βIV微管蛋白表达以及MUC5AC和DNAI1转录本。
伤口愈合后,分化为黏液细胞和纤毛细胞是可能的,并且在体外部分受到TGF-β1的抑制,TGF-β1是一种可能参与慢性气道疾病中观察到的上皮重塑的细胞因子。