Fu Xingmeng, Gong Xiaoxia, Wu Tianyi, Chen Lirou, Fu Zhou, Shu Chang
Department of Respiratory Children's Hospital of Chongqing Medical University Chongqing China.
National Clinical Research Center for Child Health and Disorders Chongqing China.
Pediatr Discov. 2024 Mar 7;2(2):e65. doi: 10.1002/pdi3.65. eCollection 2024 Jun.
The aim of this study is to research the expression of the transient receptor potential canonical channel 3 (TRPC3) in a neonatal hyperoxic lung injury model of bronchopulmonary dysplasia (BPD), and to further investigate the role of the TRPC3/nuclear factor-κB (NF-κB) signaling pathway in hyperoxia-induced BPD by a TRPC3 agonist (GSK1702934A). The hyperoxic lung injury model of BPD was established in Sprague-Dawley neonatal rats. Hematoxylin and eosin (HE) staining and radial alveolar count (RAC) values showed that the hyperoxic lung injury model of BPD was successfully established in the neonatal rats, and pulmonary edema was found in the neonatal rats with BPD. The results of reference transcriptome sequencing, Quantitative real-time PCR (qPCR), and western blot showed lower pulmonary expression of TRPC3 in the BPD group than in the control group. Immunofluorescence showed predominant expression of TRPC3 in airways and pulmonary vessels, and the fluorescence intensity of the BPD group was lower than that of the control group. Lung dry-to-wet weight ratio, HE staining, and RAC value showed that the lung histomorphology significantly improved in the BPD + TRPC3 agonist group compared with the BPD group on day 14 but did not revert to the level of the control group. According to qPCR results, compared with the control group, the expression of NF-κB1 decreased and the expression of NF-κBiz increased in the BPD group, whereas the expression of NF-κBiz decreased in the BPD + TRPC3 agonist group. Therefore, we draw the conclusion that TRPC3 may activate NF-κB by inhibiting NF-κBiz to promote cell proliferation and lung growth and development.
本研究旨在探讨瞬时受体电位阳离子通道亚家族C成员3（TRPC3）在支气管肺发育不良（BPD）新生儿高氧肺损伤模型中的表达，并通过TRPC3激动剂（GSK1702934A）进一步研究TRPC3/核因子-κB（NF-κB）信号通路在高氧诱导的BPD中的作用。在Sprague-Dawley新生大鼠中建立BPD高氧肺损伤模型。苏木精-伊红（HE）染色和肺泡计数（RAC）值显示，在新生大鼠中成功建立了BPD高氧肺损伤模型，且BPD新生大鼠出现肺水肿。参考转录组测序、定量实时聚合酶链反应（qPCR）和蛋白质免疫印迹结果显示，BPD组肺组织中TRPC3的表达低于对照组。免疫荧光显示TRPC3在气道和肺血管中主要表达，且BPD组的荧光强度低于对照组。肺干湿重比、HE染色和RAC值显示，在第14天，BPD + TRPC3激动剂组的肺组织形态学与BPD组相比有显著改善，但未恢复到对照组水平。根据qPCR结果，与对照组相比，BPD组中NF-κB1的表达降低，NF-κB2的表达升高，而在BPD + TRPC3激动剂组中NF-κB2的表达降低。因此，我们得出结论，TRPC3可能通过抑制NF-κB2来激活NF-κB，从而促进细胞增殖以及肺的生长和发育。
