Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, Qingdao, China.
Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, China.
J Biomed Mater Res A. 2024 Oct;112(10):1827-1839. doi: 10.1002/jbm.a.37730. Epub 2024 May 3.
Acute kidney injury (AKI) is a life-threatening disease primarily caused by renal ischemia-reperfusion (I/R) injury, which can result in renal failure. Currently, growth factor therapy is considered a promising and effective approach for AKI treatment. Basic fibroblast growth factor (bFGF), an angiogenic factor with potent activity, efficiently stimulates angiogenesis and facilitates regeneration of renal tissue. However, the unrestricted diffusion of bFGF restricts its clinical application in AKI treatment. Therefore, developing a novel sustained released system for bFGF could enhance its potential in treating AKI. In this study, we genetically engineered a multifunctional recombinant protein by fusing bFGF with a specific peptide (EBP). EBP-bFGF effectively binds to the extracellular matrix in the injured kidney, enabling slow release of bFGF in AKI. Furthermore, following orthotopic injection into I/R rats' ischemic kidneys, EBP-bFGF exhibited stable retention within the tissue. Additionally, EBP-bFGF suppressed apoptosis of renal cells, reduced renal fibrosis, and facilitated recovery of renal function. These findings suggest that EBP-bFGF delivery system represents a promising strategy for treating AKI.
急性肾损伤（AKI）是一种危及生命的疾病，主要由肾缺血再灌注（I/R）损伤引起，可导致肾衰竭。目前，生长因子治疗被认为是治疗 AKI 的一种有前途和有效的方法。碱性成纤维细胞生长因子（bFGF）是一种具有强大活性的血管生成因子，能有效刺激血管生成，促进肾组织再生。然而，bFGF 的无限制扩散限制了其在 AKI 治疗中的临床应用。因此，开发新型 bFGF 缓释系统可以提高其在治疗 AKI 中的潜力。在这项研究中，我们通过将 bFGF 与特定肽（EBP）融合，基因工程构建了一种多功能重组蛋白。EBP-bFGF 可有效结合损伤肾脏中的细胞外基质，使 bFGF 在 AKI 中缓慢释放。此外，EBP-bFGF 经原位注射到 I/R 大鼠缺血肾脏后，在组织内稳定保留。此外，EBP-bFGF 抑制肾细胞凋亡，减少肾纤维化，促进肾功能恢复。这些发现表明，EBP-bFGF 递药系统是治疗 AKI 的一种有前途的策略。
