Ogata-Suetsugu Saiko, Yanagihara Toyoshi, Hamada Naoki, Ikeda-Harada Chika, Yokoyama Tetsuya, Suzuki Kunihiro, Kawaguchi Tomonobu, Maeyama Takashige, Kuwano Kazuyoshi, Nakanishi Yoichi
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Biochem Biophys Res Commun. 2017 Mar 4;484(2):422-428. doi: 10.1016/j.bbrc.2017.01.142. Epub 2017 Jan 28.
As a member of the epidermal growth factor family, amphiregulin contributes to the regulation of cell proliferation. Amphiregulin was reported to be upregulated in damaged lung tissues in patients with chronic obstructive pulmonary disease and asthma and in lung epithelial cells in a ventilator-associated lung injury model. In this study, we investigated the effect of amphiregulin on lipopolysaccharide (LPS)-induced acute lung injury in mice.
Acute lung injury was induced by intranasal instillation of LPS in female C57BL/6 mice, and the mice were given intraperitoneal injections of recombinant amphiregulin or phosphate-buffered saline 6 and 0.5 h before and 3 h after LPS instillation. The effect of amphiregulin on apoptosis and apoptotic pathways in a murine lung alveolar type II epithelial cell line (LA-4 cells) were examined using flow cytometry and western blotting, respectively.
Recombinant amphiregulin suppressed epithelial cell apoptosis in LPS-induced lung injury in mice. Western blotting revealed that amphiregulin suppressed epithelial cell apoptosis by inhibiting caspase-8 activity.
Amphiregulin signaling may be a therapeutic target for LPS-induced lung injury treatment through its prevention of epithelial cell apoptosis.
双调蛋白作为表皮生长因子家族的一员,参与细胞增殖的调控。据报道,在慢性阻塞性肺疾病和哮喘患者的受损肺组织以及呼吸机相关性肺损伤模型的肺上皮细胞中,双调蛋白表达上调。在本研究中,我们调查了双调蛋白对脂多糖(LPS)诱导的小鼠急性肺损伤的影响。
通过向雌性C57BL/6小鼠鼻内滴注LPS诱导急性肺损伤,并在滴注LPS前6小时和0.5小时以及滴注后3小时给小鼠腹腔注射重组双调蛋白或磷酸盐缓冲盐水。分别使用流式细胞术和蛋白质印迹法检测双调蛋白对小鼠肺泡II型上皮细胞系(LA-4细胞)凋亡及凋亡途径的影响。
重组双调蛋白抑制了LPS诱导的小鼠肺损伤中的上皮细胞凋亡。蛋白质印迹显示,双调蛋白通过抑制半胱天冬酶-8活性抑制上皮细胞凋亡。
双调蛋白信号传导可能是通过预防上皮细胞凋亡治疗LPS诱导的肺损伤的治疗靶点。