Bi-functional KIT-PR1P peptides combine with VEGF to protect ischemic kidney in rats by targeting to Kim-1

Runxue Zhou; Hang Liu; Xianglin Hou; Qi Liu; Shuwei Sun; Xiaoge Li; Wenxuan Cao; Weihong Nie; Chunying Shi; Wei Chen

doi:10.1016/j.reth.2023.12.014

Bi-functional KIT-PR1P peptides combine with VEGF to protect ischemic kidney in rats by targeting to Kim-1

Regen Ther. 2023 Dec 28:25:162-173. doi: 10.1016/j.reth.2023.12.014. eCollection 2024 Mar.

Authors

Runxue Zhou¹, Hang Liu², Xianglin Hou³, Qi Liu^{1

4}, Shuwei Sun¹, Xiaoge Li⁵, Wenxuan Cao¹, Weihong Nie¹, Chunying Shi¹, Wei Chen⁶

Affiliations

¹ Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China.
² Department of Nephropathy, The Affiliated Hospital of Qingdao University, Qingdao, 266700, China.
³ State Key Laboratory of Molecular Developmental Biology, Institute of Genetics Cand Developmental Biology, Chinese Academy of Sciences, Beijing, 100190, China.
⁴ Department of Neurology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong, 266000, China.
⁵ Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China.
⁶ Department of Urology, Xinqiao Hospital, Army Medical University, Chongqing, 400038, China.

Abstract

Introduction: Acute kidney injury (AKI) was a disease with a high mortality mainly caused by renal ischemia/reperfusion injury (I/R). Although the current non-targeted administration of vascular endothelial growth factor (VEGF) for AKI had been revealed to facilitate the recovery of renal I/R, how to targeted deliver VEGF and to retain it efficiently in the ischemic kidney was critical for its clinical application.

Methods: In present study, bi-functional KIT-PR1P peptides were constructed which bond VEGF through PR1P domain, and targeted ischemic kidney through KIT domain to interact with biomarker of AKI-kidney injury molecule-1 (Kim-1). Then the targeted and therapeutic effects of KIT-PR1P/VEGF in AKI was explored in vitro and in vivo.

Results: The results showed KIT-PR1P exhibited better angiogenic capacity and targeting ability to hypoxia HK-2 cells with up-regulated Kim-1 in vitro. When KIT-PR1P/VEGF was used for the treatment of renal I/R through intravenous administration in vivo, KIT-PR1P could guide VEGF and retain its effective concentration in ischemic kidney. In addition, KIT-PR1P/VEGF promoted angiogenesis, alleviated renal tubular injury and fibrosis, and finally promoted functional recovery of renal I/R.

Conclusion: These results indicated that the bi-functional KIT-PR1P peptides combined with VEGF would be a promising strategy for the treatment of AKI by targeting to Kim-1.

Keywords: Acute kidney injury; Kidney injury molecular-1; Targeted delivery; Tissue regeneration; Vascular endothelial growth factor.