Modified EBP-bFGF targeting endogenous renal extracellular matrix protects against renal ischemia-reperfusion injury in rats

IF 3.9 3区医学 Q2 ENGINEERING, BIOMEDICAL Journal of biomedical materials research. Part A Pub Date : 2024-05-03 DOI:10.1002/jbm.a.37730

Xiaoge Li, Chunying Shi, Runxue Zhou, Xinhui Chen, Qingling Xu, Chunyige Zhao, Mengyao Ma, Xiang Ao, Ying Liu

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Abstract

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.

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靶向内源性肾细胞外基质的改良 EBP-bFGF 可防止大鼠肾缺血再灌注损伤

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，可导致肾功能衰竭。目前，生长因子疗法被认为是治疗急性肾损伤的一种前景广阔的有效方法。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，开发一种新型的 bFGF 持续释放系统可提高其治疗 AKI 的潜力。在这项研究中，我们通过将 bFGF 与一种特异性多肽（EBP）融合，基因工程设计了一种多功能重组蛋白。EBP-bFGF 能有效地与损伤肾脏的细胞外基质结合，使 bFGF 在 AKI 中缓慢释放。此外，将 EBP-bFGF 正位注射到 I/R 大鼠的缺血肾脏后，它能稳定地保留在组织内。此外，EBP-bFGF 还能抑制肾细胞凋亡，减少肾纤维化，促进肾功能恢复。这些研究结果表明，EBP-bFGF 输送系统是一种治疗 AKI 的有前途的策略。

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来源期刊

Journal of biomedical materials research. Part A 工程技术-材料科学：生物材料

CiteScore

10.40

自引率

2.00%

发文量

135

审稿时长

3.6 months

期刊介绍： The Journal of Biomedical Materials Research Part A is an international, interdisciplinary, English-language publication of original contributions concerning studies of the preparation, performance, and evaluation of biomaterials; the chemical, physical, toxicological, and mechanical behavior of materials in physiological environments; and the response of blood and tissues to biomaterials. The Journal publishes peer-reviewed articles on all relevant biomaterial topics including the science and technology of alloys,polymers, ceramics, and reprocessed animal and human tissues in surgery,dentistry, artificial organs, and other medical devices. The Journal also publishes articles in interdisciplinary areas such as tissue engineering and controlled release technology where biomaterials play a significant role in the performance of the medical device. The Journal of Biomedical Materials Research is the official journal of the Society for Biomaterials (USA), the Japanese Society for Biomaterials, the Australasian Society for Biomaterials, and the Korean Society for Biomaterials. Articles are welcomed from all scientists. Membership in the Society for Biomaterials is not a prerequisite for submission.