Song Siqi, Hou Xianglin, Zhang Weiwei, Liu Xinyu, Wang Wei, Wang Xiaoya, Cao Wenxuan, Xia Yujun, Chen Wei, Shi Chunying
Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao 266071, China.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, China.
Regen Biomater. 2022 May 12;9:rbac029. doi: 10.1093/rb/rbac029. eCollection 2022.
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 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 and ischemic kidneys 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.
肾缺血再灌注（I/R）损伤是急性肾损伤的主要原因之一。然而，针对这种疾病仍然没有有效的治疗方法。据报道，碱性成纤维细胞生长因子（bFGF）对缺血性疾病的恢复有益。对于肾I/R损伤治疗而言，提高bFGF的局部浓度并减少其扩散至关重要。一种能够响应再生环境中的特定生物信号以指导释放的靶向生长因子递送系统在组织修复中受到了关注。在本研究中，一种特定的肽与bFGF融合，称为bFGF-肾损伤靶向肽（KIT-bFGF），静脉注射后，该化合物在缺氧的肾HK-2细胞和缺血性肾脏中均能特异性靶向肾损伤分子-1。与天然bFGF和对照组的效果相比，当将KIT-bFGF应用于肾I/R损伤大鼠模型时，它减轻了肾小管损伤和纤维化，并促进了功能恢复。我们还研究了KIT-bFGF激活ERK1/2和Akt信号通路以显著减少细胞凋亡并保护肾脏免受缺血性损伤的机制。这些结果表明，KIT-bFGF的靶向递送可能是治疗肾I/R损伤的有效策略。
