Role of peptide KLF14-P1 in improving bronchopulmonary dysplasia by inhibiting ROS/JNK pathway
10.3760/cma.j.issn.1673-4408.2025.08.010
- VernacularTitle:多肽KLF14-P1通过抑制ROS/JNK通路改善支气管肺发育不良的作用研究
- Author:
Aoman WANG
1
;
Linmeng JIANG
;
Huaiyan WANG
;
Yu WANG
Author Information
1. 南京医科大学常州医学中心 常州市妇幼保健院新生儿科 213000
- Keywords:
Bronchopulmonary dysplasia;
Peptide;
KLF14-P1;
ROS/JNK pathway
- From:
International Journal of Pediatrics
2025;52(8):554-562
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the potential effect of peptide KLF14-P1 secreted from mesenchymal stem cells（MSCs）in bronchopulmonary dysplasia（BPD）.Methods:Low，medium and high doses of the paracrine peptide KLF14-P1 from MSCs were intraperitoneally injected into neonatal mice with BPD induced by hyperoxia. The pathological changes in lung tissue were observed，and the expression of surfactant protein C（SPC）in lung tissue was analyzed by immunofluorescence staining. Meanwhile，the levels of inflammatory factors in bronchoalveolar lavage fluid（BALF）and lung tissue，including tumor necrosis factor alpha（TNF-α），interleukin-1β（IL-1β），IL-6，and IL-10，were detected. And after pretreating with low，medium and high doses of KLF14-P1 for 24 hours，mouse lung epithelial cells MLE-12 were stimulated with H 2O 2 for 2 hours. The cell proliferation，levels of inflammatory factors（TNF-α，IL-1β，IL-6，IL-10），reactive oxygen species（ROS），and c-Jun N-terminal kinase（JNK）protein level were then detected. Results:The lung dry-to-wet weight ratio of the medium-dose KLF14-P1 group（0.202±0.011）and the high-dose KLF14-P1 group（0.209±0.010）of the newborn mice increased significantly compared with the BPD group（0.187±0.008）（ P<0.01）. Compared with the BPD group，the lung alveolar structure of the newborn mice in the medium-dose and high-dose KLF14-P1 groups improved significantly，and the levels of TNF-α，IL-1β，and IL-6 in lung tissue and BALF decreased，while IL-10 increased（all P< 0.01）. Compared with the H 2O 2 group（49.296%±0.980%），the survival rate of MLE-12 cells in the low-dose group（56.390%±0.810%），the medium-dose group（73.506%±2.504%），and the high-dose group（81.699%±1.554%）increased significantly，cell apoptosis decreased significantly，inflammatory factors TNF-α，IL-1β，and IL-6 decreased，and IL-10 level increased（all P<0.01）. Moreover，the ROS accumulation of cells in the low，medium，and high-dose KLF14-P1 groups was lower than that of the H 2O 2 group，and the phosphorylated JNK protein level decreased（all P<0.05）. Conclusion:KLF14-P1 alleviated the lung injury and inflammatory response in BPD mouse，possibly through the inhibition of the ROS/JNK pathway.
