Zhang Jiaojiao, Zhou Jinrun, Yu Yifan, Cai Yuqing, Li Zhiliang, Lu Yao, Zhao Jing
Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, 266237, People's Republic of China.
Lung. 2023 Feb;201(1):65-77. doi: 10.1007/s00408-023-00598-7. Epub 2023 Feb 3.
Acute lung injury (ALI) with high rates of morbidity is often accompanied by the apoptosis in the type I alveolar epithelial cells (ATIs). Thus, the transdifferentiation of type II alveolar epithelial cells (ATIIs) into ATIs is crucial for the maintenance of alveolar epithelial functions. We aimed to elucidate the role of sesamin in the transdifferentiation of ATIIs to ATIs and the involvement of the TRPV1/AKT pathway.
In vivo, the mouse model of ALI was simulated by intraperitoneal and intratracheal injections of lipopolysaccharide (LPS), respectively. The protective effects of sesamin on ALI were investigated using the survival rate, lung/body weight ratio, histological analysis of lung with HE staining, and mRNA levels of inflammatory factors. Western blot analysis and immunofluorescence detection of ATIs marker AQP5 were used to evaluate the protective effect of sesamin on ATIs. Western blot, EdU, and qPCR analyses were applied to detect changes in apoptosis, proliferation, and transdifferentiation markers of ATII A549 cell lines. Small interfering RNA (siRNA) was used to detect the involvement and relationships between the sesamin receptors (ANXA1 and TRPV1) and the AKT pathway in transdifferentiation.
Sesamin (200 mg/kg) significantly improved LPS-induced ALI and inhibited LPS-induced ATIs reduction. A low concentration of sesamin (20 μM) promoted the transdifferentiation of ATIIs to ATIs. Both ANXA1 and TRPV1 were involved in sesamin-promoted transdifferentiation, while the P-AKT (S473) level was down-regulated by TRPV1 siRNA.
Sesamin may promote transdifferentiation of ATII to ATI to ultimately rescue ALI, with TRPV1/AKT pathway involved in this transdifferentiation. This study revealed a novel role of sesamin in promoting the transdifferentiation of ATIIs to ATIs, providing experimental supports for the potential targets of ALI therapy.
发病率较高的急性肺损伤（ALI）常伴有I型肺泡上皮细胞（ATIs）凋亡。因此，II型肺泡上皮细胞（ATIIs）向ATIs的转分化对于维持肺泡上皮功能至关重要。我们旨在阐明芝麻素在ATIIs向ATIs转分化中的作用以及TRPV1/AKT通路的参与情况。
在体内，分别通过腹腔注射和气管内注射脂多糖（LPS）模拟ALI小鼠模型。使用存活率、肺/体重比、HE染色的肺组织学分析以及炎症因子的mRNA水平来研究芝麻素对ALI的保护作用。采用蛋白质免疫印迹分析和ATIs标志物AQP5的免疫荧光检测来评估芝麻素对ATIs的保护作用。应用蛋白质免疫印迹、EdU和qPCR分析来检测ATII A549细胞系凋亡、增殖和转分化标志物的变化。使用小干扰RNA（siRNA）来检测芝麻素受体（ANXA1和TRPV1）与转分化中AKT通路之间的参与情况和关系。
芝麻素（200mg/kg）显著改善了LPS诱导的ALI，并抑制了LPS诱导的ATIs减少。低浓度的芝麻素（20μM）促进了ATIIs向ATIs的转分化。ANXA1和TRPV1均参与了芝麻素促进的转分化，而TRPV1 siRNA下调了P-AKT（S473）水平。
芝麻素可能促进ATII向ATI的转分化，最终挽救ALI，TRPV1/AKT通路参与了这种转分化。本研究揭示了芝麻素在促进ATIIs向ATIs转分化中的新作用，为ALI治疗的潜在靶点提供了实验支持。
