Xu Panpan, Zhuo Wanqing, Zhang Peipei, Chen Ying, Du Yue, Li Ying, Wang Yajuan
Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100020, China.
School of Life Sciences, Peking University, Beijing 100871, China.
Biomolecules. 2025 Jan 10;15(1):101. doi: 10.3390/biom15010101.
Disrupted neonatal lung alveologenesis often leads to bronchopulmonary dysplasia (BPD), the most common chronic lung disease in children. The inhibition of type 2 alveolar (AT2) cell proliferation plays an important role in the arrest of alveologenesis. However, the mechanism of AT2 cell proliferation retardation in BPD is still not fully elucidated. The purpose of the present study was to explore the effects of cyclin G1 (CCNG1) on AT2 cell proliferation in hyperoxia-induced lung injury in neonatal mice. Our findings revealed that hyperoxia significantly reduced the proportion of AT2 cells in the lungs of neonatal mice and coincided with an upregulation of CCNG1 expression. Notably, this upregulation of CCNG1 was accompanied by an increase in Wnt signaling. We observed colocalization of CCNG1 and Wnt3a within AT2 cells in the hyperoxia group. Further analysis showed that inhibiting CCNG1 expression regressed the expression of Wnt signaling and enhanced cell proliferation. These results suggest that CCNG1 plays a pivotal role in suppressing AT2 cell proliferation, at least partly by counteracting the effects of Wnt signaling to modulate AT2 cell growth in the BPD model. Our findings contribute to a better understanding of the mechanisms underlying BPD.
新生儿肺泡形成障碍常导致支气管肺发育不良（BPD），这是儿童中最常见的慢性肺部疾病。2型肺泡上皮细胞（AT2）增殖的抑制在肺泡形成停滞中起重要作用。然而，BPD中AT2细胞增殖迟缓的机制仍未完全阐明。本研究的目的是探讨细胞周期蛋白G1（CCNG1）对新生小鼠高氧诱导肺损伤中AT2细胞增殖的影响。我们的研究结果显示，高氧显著降低了新生小鼠肺中AT2细胞的比例，同时CCNG1表达上调。值得注意的是，CCNG1的这种上调伴随着Wnt信号的增加。我们在高氧组的AT2细胞中观察到CCNG1和Wnt3a的共定位。进一步分析表明，抑制CCNG1表达可使Wnt信号的表达回归并增强细胞增殖。这些结果表明，CCNG1在抑制AT2细胞增殖中起关键作用，至少部分是通过抵消Wnt信号的作用来调节BPD模型中AT2细胞的生长。我们的研究结果有助于更好地理解BPD的潜在机制。
