Angiogenesis-promoting effect of SKP-SC-EVs-derived miRNA-30a-5p in peripheral nerve regeneration by targeting LIF and ANGPT2
Ischemia and hypoxia caused by vascular injury intensify nerve damage. Skin precursor-derived Schwann cells have demonstrated an accelerated in vivo prevascularization of tissue-engineered nerves. Furthermore, extracellular vesicles from skin precursor-derived Schwann cells (SKP-SC-EVs) show the potential in aiding peripheral nerve regeneration. Nonetheless, the capacity of SKP-SC-EVs to facilitate nerve repair via angiogenesis remains uncertain. This study observed that SKP-SC-EVs significantly enhanced angiogenesis, evidenced by increased transparency of the tissue-engineered nerve graft and ultrasonic blood flow imaging. In vitro experiments confirmed that SKP-SC-EVs promote the proliferation, migration, and tube formation of human umbilical vein endothelial cells, a standard model for assessing angiogenic potential. Additionally, a comprehensive miRNA expression profile of SKP-SC-EVs was performed, leading to the identification of potential candidates through functional experiments. Among these, miR-30a-5p emerged as a significant candidate, demonstrating remarkable proangiogenic effects both in vivo and in vitro, akin to the effects of SKP-SC-EVs. Furthermore, luciferase reporter assay and functional experiments revealed that miR-30a-5p in SKP-SC-EVs promotes angiogenesis by targeting ANGPT2 and LIF without sufficient VEGFa. Thus, the enrichment of miR-30a-5p in SKP-SC-EVs indicates its pivotal role as a regulator of angiogenesis, presenting a promising avenue for cell-free treatment of peripheral nerve injury.
Authors
- Shu‐Yu Zhang (ORCID: https://orcid.org/0000-0002-1811-4159)
- Mi Shen (ORCID: https://orcid.org/0000-0002-3605-0419)
- Mingzhi Du
- Hualin Sun (ORCID: https://orcid.org/0000-0003-1889-1561)
- Xinli Ye (ORCID: https://orcid.org/0000-0002-7032-2000)
- Yujiao Ye (ORCID: https://orcid.org/0000-0003-0079-7630)
- Yi Lu (ORCID: https://orcid.org/0000-0002-0675-1695)
- Leilei Gong (ORCID: https://orcid.org/0000-0002-6976-1372)
- Jiahuan Gong
- Jin‐Hua Gu (ORCID: https://orcid.org/0000-0002-5177-8352)
- Lijuan Wang (ORCID: https://orcid.org/0000-0002-5439-8988)
- Songlin Zhou (ORCID: https://orcid.org/0000-0001-8598-0922)
- Mengru Zheng
- Jian Zhao (ORCID: https://orcid.org/0000-0001-9474-3099)
- Qianru He (ORCID: https://orcid.org/0000-0002-7924-7545)
- Xiaosong Gu (ORCID: https://orcid.org/0000-0002-2562-6275)
- Wenqing Xu (ORCID: https://orcid.org/0009-0007-4979-6491)
- Chang Liu (ORCID: https://orcid.org/0000-0003-3085-4202)
- Qi Zhang (ORCID: https://orcid.org/0000-0001-7599-6533)
- Ning Zhang (ORCID: https://orcid.org/0000-0002-9513-9288)
- Zhen Xu (ORCID: https://orcid.org/0009-0001-2039-7805)
- Min Feng (ORCID: https://orcid.org/0000-0001-6427-3612)
- Huimin Xie (ORCID: https://orcid.org/0000-0002-5717-5034)
- Jiyu Li (ORCID: https://orcid.org/0000-0002-3805-7729)
- Yibin Wang (ORCID: https://orcid.org/0000-0003-0852-0767)
- Qiang Zhou (ORCID: https://orcid.org/0000-0002-6237-8813)
- Cong Meng
- Miaomei Yu (ORCID: https://orcid.org/0000-0002-8287-0725)
- Yingjie Xia (ORCID: https://orcid.org/0000-0003-1161-0560)
- Xing‐Jun Liu (ORCID: https://orcid.org/0000-0002-5496-541X)
- Chunyan Deng (ORCID: https://orcid.org/0000-0001-5581-9417)
- Junjie Kong
- Fei Ding (ORCID: https://orcid.org/0000-0002-1636-6854)
Institutions
- Nantong University (CN)
- Soochow University (CN)
- Nantong Maternity and Child Health Hospital (CN)
- Affiliated Hospital of Nantong University (CN)
- Shanghai Changzheng Hospital (CN)
- Shanghai First People's Hospital (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- Journal of Biological Chemistry
- Published
- 2024-12-26
- DOI
- https://doi.org/10.1016/j.jbc.2024.108146
- Citations
- 7
- Primary Topic
- Nerve injury and regeneration
- Type
- article
- Field-Weighted Citation Impact
- 1.88
Funders
- Jiangsu Commission of Health
- National Natural Science Foundation of China
- Government of Jiangsu Province
- Nantong University
- Priority Academic Program Development of Jiangsu Higher Education Institutions