Department of Pediatrics, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, Anhui, People's Republic of China.
Mol Biotechnol. 2024 Sep;66(9):2349-2361. doi: 10.1007/s12033-023-00866-0. Epub 2023 Sep 14.
Bronchopulmonary dysplasia (BPD), caused by hyperoxia exposure, is the most common complication affecting preterm infants. The C-X-C motif chemokine ligand 17 (CXCL17) belongs to the chemokine family that plays important roles in various processes, but the function in BPD is unknown. Elevated serum CXCL17 levels were observed in human premature infants with hyperoxia-induced lung injury, suggesting that CXCL17 might be involved in BPD. To further validate our speculation, studies were conducted in a hyperoxia-induced lung injury mouse model and primary murine alveolar epithelial cells Type II (T2AEC) cells exposed to hyperoxia. RT-qPCR and western blot were used to validate CXCL17 expression in newborn mice. Hyperoxia exposure-induced lung injury was determined by assessing the lung wet-weight/dry-weight ratio and histological changes. Oxidative stress and inflammatory factors were examined by ELISA assay and RT-qPCR. Reactive oxygen species (ROS) level was evaluated by DHE staining. Apoptosis was assessed by TUNEL staining and western blot. The results showed that hyperoxia exposure increased CXCL17 levels in newborn mice pups. Hyperoxia exposure increased lung wet-weight/dry-weight ratio, increased alveolar diameter and enlarged alveoli, and reduced surfactant protein C expression. However, recombinant CXCL17 (rCXCL17) treatment alleviated hyperoxia-induced lung injury. rCXCL17 treatment inhibited hyperoxia-induced inflammation, oxidative stress, and apoptosis in neonatal mice. These results were further verified in T2AEC cells. Additionally, rCXCL17 treatment activated the AKT pathway, which is a protective pathway in BPD. Collectively, rCXCL17 alleviates hyperoxia-induced lung injury in neonatal mice by activating the AKT pathway, indicating that CXCL17 may be a promising target for BPD therapy.
支气管肺发育不良（BPD）是由高氧暴露引起的，是影响早产儿最常见的并发症。C-X-C 基序趋化因子配体 17（CXCL17）属于趋化因子家族，在各种过程中发挥重要作用，但在 BPD 中的功能尚不清楚。在高氧诱导的肺损伤的人类早产儿中观察到血清 CXCL17 水平升高，提示 CXCL17 可能参与 BPD。为了进一步验证我们的推测，在高氧诱导的肺损伤小鼠模型和高氧暴露的原代小鼠肺泡上皮细胞 II 型（T2AEC）细胞中进行了研究。RT-qPCR 和 Western blot 用于验证新生小鼠中 CXCL17 的表达。通过评估肺湿重/干重比和组织学变化来确定高氧暴露诱导的肺损伤。通过 ELISA 测定和 RT-qPCR 检测氧化应激和炎症因子。通过 DHE 染色评估活性氧（ROS）水平。通过 TUNEL 染色和 Western blot 评估细胞凋亡。结果表明，高氧暴露增加了新生小鼠幼仔的 CXCL17 水平。高氧暴露增加了肺湿重/干重比，增加了肺泡直径和扩大的肺泡，并降低了表面活性蛋白 C 的表达。然而，重组 CXCL17（rCXCL17）治疗减轻了高氧诱导的肺损伤。rCXCL17 治疗抑制了新生小鼠的高氧诱导的炎症、氧化应激和细胞凋亡。这些结果在 T2AEC 细胞中得到了进一步验证。此外，rCXCL17 治疗激活了 AKT 通路，该通路是 BPD 中的一种保护通路。总之，rCXCL17 通过激活 AKT 通路减轻新生小鼠的高氧诱导的肺损伤，表明 CXCL17 可能是治疗 BPD 的有前途的靶标。
