Bi-functional KIT-PR1P peptides combine with VEGF to protect ischemic kidney in rats by targeting to Kim-1
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 t...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Regenerative Therapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320423001475 |
| _version_ | 1797269009829199872 |
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| author | Runxue Zhou Hang Liu Xianglin Hou Qi Liu Shuwei Sun Xiaoge Li Wenxuan Cao Weihong Nie Chunying Shi Wei Chen |
| author_facet | Runxue Zhou Hang Liu Xianglin Hou Qi Liu Shuwei Sun Xiaoge Li Wenxuan Cao Weihong Nie Chunying Shi Wei Chen |
| author_sort | Runxue Zhou |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T18:43:23Z |
| format | Article |
| id | doaj.art-e2cf6565adec4f6d982d3625fa44c2f9 |
| institution | Directory Open Access Journal |
| issn | 2352-3204 |
| language | English |
| last_indexed | 2024-04-25T01:41:34Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj.art-e2cf6565adec4f6d982d3625fa44c2f92024-03-08T05:18:48ZengElsevierRegenerative Therapy2352-32042024-03-0125162173Bi-functional KIT-PR1P peptides combine with VEGF to protect ischemic kidney in rats by targeting to Kim-1Runxue Zhou0Hang Liu1Xianglin Hou2Qi Liu3Shuwei Sun4Xiaoge Li5Wenxuan Cao6Weihong Nie7Chunying Shi8Wei Chen9Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266071, ChinaDepartment of Nephropathy, The Affiliated Hospital of Qingdao University, Qingdao, 266700, ChinaState Key Laboratory of Molecular Developmental Biology, Institute of Genetics Cand Developmental Biology, Chinese Academy of Sciences, Beijing, 100190, ChinaDepartment of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China; Department of Neurology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong, 266000, ChinaDepartment of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266071, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, Qingdao, 266071, ChinaDepartment of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266071, ChinaDepartment of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266071, ChinaDepartment of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China; Corresponding author.Department of Urology, Xinqiao Hospital, Army Medical University, Chongqing, 400038, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2352320423001475Vascular endothelial growth factorAcute kidney injuryTargeted deliveryKidney injury molecular-1Tissue regeneration |
| spellingShingle | Runxue Zhou Hang Liu Xianglin Hou Qi Liu Shuwei Sun Xiaoge Li Wenxuan Cao Weihong Nie Chunying Shi Wei Chen Bi-functional KIT-PR1P peptides combine with VEGF to protect ischemic kidney in rats by targeting to Kim-1 Regenerative Therapy Vascular endothelial growth factor Acute kidney injury Targeted delivery Kidney injury molecular-1 Tissue regeneration |
| title | Bi-functional KIT-PR1P peptides combine with VEGF to protect ischemic kidney in rats by targeting to Kim-1 |
| title_full | Bi-functional KIT-PR1P peptides combine with VEGF to protect ischemic kidney in rats by targeting to Kim-1 |
| title_fullStr | Bi-functional KIT-PR1P peptides combine with VEGF to protect ischemic kidney in rats by targeting to Kim-1 |
| title_full_unstemmed | Bi-functional KIT-PR1P peptides combine with VEGF to protect ischemic kidney in rats by targeting to Kim-1 |
| title_short | Bi-functional KIT-PR1P peptides combine with VEGF to protect ischemic kidney in rats by targeting to Kim-1 |
| title_sort | bi functional kit pr1p peptides combine with vegf to protect ischemic kidney in rats by targeting to kim 1 |
| topic | Vascular endothelial growth factor Acute kidney injury Targeted delivery Kidney injury molecular-1 Tissue regeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2352320423001475 |
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