Ferrera Loretta, Capurro Valeria, Delpiano Livia, Gianotti Ambra, Moran Oscar
U.O.C. Genetica Medica, Istituto G. Gaslini, Via G. Gaslini, 5, 16148 Genoa, Italy.
Istituto di Biofisica, CNR, Via De Marini, 6, 16149 Genoa, Italy.
Biology (Basel). 2021 Mar 29;10(4):278. doi: 10.3390/biology10040278.
Cystic fibrosis (CF) is a genetic disease associated with the defective function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein that causes obstructive disease and chronic bacterial infections in airway epithelia. Deletion of phenylalanine at position 508, p.F508del, the most frequent mutation among CF patients, causes a folding and traffic defect, resulting in a dramatic reduction in the CFTR expression. To investigate whether the direct application of bicarbonate could modify the properties of the airway surface liquid (ASL), we measured the micro-viscosity, fluid transport and pH of human bronchial epithelial cells monolayers. We have demonstrated that the treatment of a CF-epithelia with an iso-osmotic solution containing bicarbonate is capable of reducing both, the ASL viscosity and the apical fluid re-absorption. We suggest the possibility of design a supportive treatment based on topical application of bicarbonate, or any other alkaline buffer.
囊性纤维化(CF)是一种与囊性纤维化跨膜传导调节因子(CFTR)蛋白功能缺陷相关的遗传性疾病,该蛋白功能缺陷会导致气道上皮出现阻塞性疾病和慢性细菌感染。苯丙氨酸508位缺失(p.F508del)是CF患者中最常见的突变,会导致折叠和转运缺陷,从而使CFTR表达显著降低。为了研究直接应用碳酸氢盐是否能改变气道表面液体(ASL)的特性,我们测量了人支气管上皮细胞单层的微粘度、液体转运和pH值。我们已经证明,用含碳酸氢盐的等渗溶液处理CF上皮细胞能够降低ASL粘度和顶端液体重吸收。我们提出了基于局部应用碳酸氢盐或任何其他碱性缓冲液设计支持性治疗的可能性。