Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (10): 2260-2267.doi: 10.4103/1673-5374.369119

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A new peptide, VD11, promotes structural and functional recovery after spinal cord injury

Shan-Shan Li1, #, Bai-Yu Zhang3, 4, #, Sai-Ge Yin1, Zi-Qi Wei1, Nai-Xin Liu1, Yi-Lin Li1, Si-Yu Wang1, Yu-Heng Shi1, Jian Zhao1, Li-Juan Wang1, Yue Zhang1, Jun Sun1, *, Ying Wang2, *, Xin-Wang Yang1, *#br#   

  1. 1Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan Province, China; 2Key Laboratory of Chemistry in Ethnic Medicinal Resources & Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming, Yunnan Province, China; 3Department of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China; 4Yunnan Province Clinical Research Center for Chronic Kidney Disease, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
  • Online:2023-10-15 Published:2023-03-28
  • Contact: Xin-Wang Yang, PhD, yangxinwanghp@163.com or yangxinwang@kmmu.edu.cn; Ying Wang, PhD, wangying_814@163.com; Jun Sun, BS, sunjun6661@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 32060212 (to YW), 81760648 (to XWY), 81560118 (to BYZ); Project of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation, Nos. 202101AY070001-006 (to XWY) and 2018FE001 (-161) (to JS); Yunnan Applied Basic Research Project Foundation, No. 2019FB128 (to YW); Project of Yunnan Province Clinical Research Center for Chronic Kidney Disease, No. 202102AA10060 (to BYZ); a grant from Scientific Research Foundation of Department of Education of Yunnan Province, No. 2021J0205 (to SSL). 

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Abstract: The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury. It is therefore a priority to develop new drugs that can promote structural and functional recovery after spinal cord injury. Previous studies have shown that peptides can promote substantial repair and regeneration of injured tissue. While amphibians have a pronounced ability to regenerate the spinal cord, few studies have investigated the effect of amphibian spinal cord-derived peptides on spinal cord injury. Here we report for the first time the successful identification and isolation of a new polypeptide, VD11 (amino acid sequence: VDELWPPWLPC), from the spinal cord of an endemic Chinese amphibian (Odorrana schmackeri). In vitro experiments showed that VD11 promoted the secretion of nerve growth factor and brain-derived neurotrophic factor in BV2 cells stimulated with lipopolysaccharide, as well as the proliferation and synaptic elongation of PC12 cells subjected to hypoxia. In vivo experiments showed that intravertebral injection of VD11 markedly promoted recovery of motor function in rats with spinal cord injury, alleviated pathological damage, and promoted axonal regeneration. Furthermore, RNA sequencing and western blotting showed that VD11 may affect spinal cord injury through activation of the AMPK and AKT signaling pathways. In summary, we discovered a novel amphibian-derived peptide that promotes structural and functional recovery after spinal cord injury. 

Key words: Akt signaling pathway, amphibian-derived bioactive peptide, AMPK signaling pathway, axonal regeneration, brain-derived neurotrophic factor, ischemia/reperfusion injury, motor function, nerve growth factor, neuroprotective effect, spinal cord injury