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Specific bFGF targeting of KIM-1 in ischemic kidneys protects against renal ischemia-reperfusion injury in rats

查看全文 作　　者：Siqi [1]Song;Xianglin [2]Hou;Weiwei [3]Zhang;Xinyu [1]Liu;Wei [1]Wang;Xiaoya [1]Wang;Wenxuan [1]Cao;Yujun [1]Xia;Wei [4]Chen;Chunying [1]Shi 高影响力作者 机构地区：[1]Department of Human Anatomy,Histology and Embryology,School of Basic Medicine,Qingdao University,Qingdao 266071,China;[2]State Key Laboratory of Molecular Developmental Biology,Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing 100190,China;[3]Department of Nephrology,Army Medical Center of PLA,Army Medical University,Chongqing 400038,China;[4]Department of Urology,Xinqiao Hospital,Army Medical University,Chongqing 400038,China高影响力机构 出　　处：《Regenerative Biomaterials》索引2022年第9卷第1期,共12页高影响力期刊 基　　金：supported by the National Natural Science Foundation of China(81970590,31670989);the Key Research and Development Program of Shandong Province(2019GSF107037). 摘　　要：Renal ischemia-reperfusion(I/R)injury is one of the major causes of acute kidney injury.However,there is still no effective treatment for this disease.Basic fibroblast growth factor(bFGF)has been reported to be beneficial for recovery from ischemic diseases.It is vital to increase the local concentration and reduce the diffusion of bFGF in vivo for renal I/R injury therapy.A targeted growth factor delivery system that responds to specific biological signals in the regenerative environment to guide release has been highlighted in tissue repair.In the present study,a specific peptide was fused with bFGF and called bFGF-kidney injury targeting(KIT-bFGF),and this compound specifically targeted kidney injury molecule-1 both in hypoxic renal HK-2 cells in vitro and ischemic kidneys in vivo after intravenous injection.When administered to rat models of renal I/R injury,KIT-bFGF attenuated renal tubule damage and fibrosis,and promoted functional recovery compared to the effects of native bFGF and the control.We also investigated the mechanism by which KIT-bFGF activated the ERK1/2 and Akt signaling pathways to significantly reduce apoptosis and protect against ischemic injury in the kidney.These results demonstrated that targeted delivery of KIT-bFGF could be an effective strategy for the treatment of renal I/R injury. 关 键 词：basic fibroblast growth factor acute kidney injury targeted therapy growth factor delivery system
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