去除脂肪型脂肪酸结合蛋白4阳性干细胞可影响肺部无纤毛(clara)细胞的增殖与自我更新

Removal of fatty acid-binding protein 4 positive stem cells affects the proliferation and self-renewal capability of clara cells in the lung

背景:近年来关于脂肪型脂肪酸结合蛋白4(fatty acid-binding protein 4,FABP4)的研究已经很多,但肺中FABP4的表达情况与功能仍不明确。目的:探究FABP4在肺中的表达情况和功能。方法:利用FABP4 Cre; Rosa26-tdTomato小鼠示踪红色荧光蛋白表达以及免疫荧光染色共定位系统性地研究了FABP4在肺中的表达情况,并构建FABP4 Cre; iDTR转基因小鼠通过注射白喉毒素特异性去除肺部表达FABP4的细胞,初步探究FABP4在肺中的功能。结果与结论:FABP4能标记成年小鼠肺部的巨噬细胞、无纤毛(clara)细胞、Ⅱ型肺泡细胞、PDGFRα和vimentin阳性间质细胞,但不能标记平滑肌细胞和纤毛(ciliated)细胞。另外,当去除肺部表达FABP4阳性细胞时会出现小鼠无纤毛(clara)细胞及纤毛(ciliated)细胞比例减少的表型,推测可能是去除了FABP4阳性干细胞特性细胞后影响了肺部无纤毛(clara)细胞的增殖与自我更新。该研究比较全面地揭示了FABP4在小鼠肺中的表达情况,并初步探究了FABP4在肺中的作用,为肺的免疫反应及稳态维持等相关研究奠定了一定的基础,并可能成为肺部疾病治疗的潜在靶点。

BACKGROUND: In recent years, there have been many studies about fatty acid-binding protein 4(FABP4);however, few studies focus on the expression and function of FABP4 in the lung.OBJECTIVE: To systematically explore the expression and function of FABP4 in the lung.METHODS: FABP4 Cre;Rosa26-tdTomato mice were selected to trace red fluorescent protein expression and immunofluorescence co-localization analysis was used to systematically detect the expression of FABP4 in the lung. We made a further study on function of FABP4 in lung by constructing FABP4 Cre;iDTR transgenic mice injected with diphtheria toxin to remove the FABP4^+ cells from the lung.RESULTS AND CONCLUSION: FABP4 could label macrophages, clara cells, type Ⅱ alveolar cells, PDGFRα+ and vimentin+ mesenchymal cells in the lung of adult mice, and could not label smooth muscle cells and ciliated cells. In addition, percentages of clara cells and ciliated cells decreased when the FABP4^+ cells were removed from the lung. We supposed that removal of FABP4^+ cells with stem cell characteristics could influence the proliferation and self-renewal of clara cells in the lung. This study comprehensively revealed the expression pattern of FABP4 in lung of mice and preliminarily explored the FABP4 function in the lung, laying a foundation for the study of pulmonary immune response and homeostasis maintenance. Moreover, FABP4 may become a potential target for the treatment of lung diseases.