Wang Yueming, Li Chunsun, Wu Zhen, Dai Yu, Liu Lu, Chen Liangan
School of Medicine, Nankai University, Tianjin, China.
Department of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing, China.
J Thorac Dis. 2023 Mar 31;15(3):1445-1459. doi: 10.21037/jtd-23-293. Epub 2023 Mar 24.
Previous studies of lung cancer metastasis-related protein 1 () mainly focused on its relationship with cancer. However, the function of in normal tissues or cells is poorly understood. We aimed to investigate the effects of alveolar type II cell (AT2 cell)-specific deletion on lung structure and function in adult mice.
Mice carrying the floxed allele with exons 2-4 flanked by loxP sites were constructed and then crossed with mice to obtain ; for AT2 cell-specific deletion and mice as littermate control. We observed the body weight change, histopathology, lung wet/dry weight ratio, pulmonary function, and survival of the mice, together with the protein concentration, inflammatory cells, and cytokine levels in bronchoalveolar lavage fluid. We also detected AT2 cell numbers and expression of pulmonary surfactant protein in the lung tissues. The apoptosis of AT2 cells was also assessed.
We found that AT2 cell-specific deletion caused rapid weight loss and increased mortality in mice. Histopathological analysis revealed damaged lung structure, including inflammatory cell infiltration, alveolar hemorrhage, and edema. The lung wet/dry weight ratio was higher and bronchoalveolar lavage fluid (BALF) analysis revealed elevated protein concentration, inflammatory cell counts, and cytokine levels. Pulmonary function measurement showed increased airway resistance, decreased lung compacity, and compliance. We also found massive AT2 cell loss and altered expression of pulmonary surfactant protein. Deletion of promoted apoptosis in AT2 cells.
We successfully generated an AT2 cell-specific conditional knockout mouse model and further revealed the crucial role of in maintaining AT2 cell homeostasis.
先前关于肺癌转移相关蛋白1（）的研究主要集中在其与癌症的关系上。然而，在正常组织或细胞中的功能尚不清楚。我们旨在研究成年小鼠肺泡Ⅱ型细胞（AT2细胞）特异性缺失对肺结构和功能的影响。
构建携带loxP位点侧翼的外显子2 - 4的floxed等位基因的小鼠，然后与小鼠杂交以获得；用于AT2细胞特异性缺失，以及作为同窝对照的小鼠。我们观察了小鼠的体重变化、组织病理学、肺湿/干重比、肺功能和存活率，以及支气管肺泡灌洗液中的蛋白质浓度、炎症细胞和细胞因子水平。我们还检测了肺组织中AT2细胞数量和肺表面活性物质蛋白的表达。还评估了AT2细胞的凋亡情况。
我们发现AT2细胞特异性缺失导致小鼠体重快速减轻和死亡率增加。组织病理学分析显示肺结构受损，包括炎症细胞浸润、肺泡出血和水肿。肺湿/干重比更高，支气管肺泡灌洗液（BALF）分析显示蛋白质浓度、炎症细胞计数和细胞因子水平升高。肺功能测量显示气道阻力增加、肺容量和顺应性降低。我们还发现大量AT2细胞丢失和肺表面活性物质蛋白表达改变。的缺失促进了AT2细胞的凋亡。
我们成功构建了AT2细胞特异性条件性敲除小鼠模型，并进一步揭示了在维持AT2细胞稳态中的关键作用。
