Human breast milk-derived exosomes through inhibiting AT II cell apoptosis to prevent bronchopulmonary dysplasia in rat lung

Zhou, Yahui1,2; Liu, Yiwen1,3; Xu, Gen1,4; Liu, Lingjie1; Li, Huimin1; Li, Yubai3; Yin, Jing1; Wang, Xingyun1; Yu, Zhangbin1,5,6

2022-07-01

10.1111/jcmm.17334

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE   Impact Factor & Quartile

1582-1838

1582-4934

Human breast milk (HBM) effectively prevents and cures neonatal bronchopulmonary dysplasia (BPD). Exosomes are abundant in breast milk, but the function of HBM-derived exosomes (HBM-Exo) in BPD is still unclear. This study was to investigate the role and mechanism of HBM-Exo in BPD. Overall lung tissue photography and H&E staining showed that HBM-Exo improved the lung tissue structure collapse, alveolar structure disorder, alveolar septum width, alveolar number reduction and other injuries caused by high oxygen exposure. Immunohistochemical results showed that HBM-Exo improved the inhibition of cell proliferation and increased apoptosis caused by hyperoxia. qPCR and Western blot results also showed that HBM-Exo improved the expression of Type II alveolar epithelium (AT II) surface marker SPC. In vivo study, CCK8 and flow cytometry showed that HBM-Exo improved the proliferation inhibition and apoptosis of AT II cells induced by hyperoxia, qPCR and immunofluorescence also showed that HBM-Exo improved the down-regulation of SPC. Further RNA-Seq results in AT II cells showed that a total of 88 genes were significantly different between the hyperoxia and HBM-Exo with hyperoxia groups, including 24 up-regulated genes and 64 down-regulated genes. KEGG pathway analysis showed the enrichment of IL-17 signalling pathway was the most significant. Further rescue experiments showed that HBM-Exo improved AT II cell damage induced by hyperoxia through inhibiting downstream of IL-17 signalling pathway (FADD), which may be an important mechanism of HBM-Exo in the prevention and treatment of BPD. This study may provide new approach in the treatment of BPD.

apoptosis AT II bronchopulmonary dysplasia FADD HBM-Exo IL-17

SCI

English

Corresponding

National Natural Science Foundation of China["8190512","82001597"] ; Top medical expert team of Wuxi Taihu Talent Program[DJTD202106]

Cell Biology ; Research & Experimental Medicine

Cell Biology ; Medicine, Research & Experimental

WOS:000825739500001

WILEY

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Womens Hosp, Dept Pediat, 123rd Tian Fei Xiang,Mo Chou Rd, Nanjing 210004, Jiangsu, Peoples R China
2.Nanjing Med Univ, Wuxi Childrens Hosp, Dept Neonatol, Wuxi, Jiangsu, Peoples R China
3.Xuzhou Med Univ, Affiliated Hosp, Xuzhou, Jiangsu, Peoples R China
4.Nanjing Med Univ, Affiliated Hosp 1, Dept Cardiothorac Surg, Nanjing, Jiangsu, Peoples R China
5.Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp, Dept Neonatol, Shenzhen, Guangdong, Peoples R China
6.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen, Guangdong, Peoples R China

Zhou, Yahui,Liu, Yiwen,Xu, Gen,et al. Human breast milk-derived exosomes through inhibiting AT II cell apoptosis to prevent bronchopulmonary dysplasia in rat lung[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2022.

Zhou, Yahui.,Liu, Yiwen.,Xu, Gen.,Liu, Lingjie.,Li, Huimin.,...&Yu, Zhangbin.(2022).Human breast milk-derived exosomes through inhibiting AT II cell apoptosis to prevent bronchopulmonary dysplasia in rat lung.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE.

Zhou, Yahui,et al."Human breast milk-derived exosomes through inhibiting AT II cell apoptosis to prevent bronchopulmonary dysplasia in rat lung".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2022).