School of Basic Medicine, Medical College, Qingdao University, Qingdao, Shandong 266071, P.R. China.
Department of Gynaecology and Obstetrics, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China.
Mol Med Rep. 2022 Nov;26(5). doi: 10.3892/mmr.2022.12842. Epub 2022 Sep 7.
Liver regeneration is a complex process that needs orchestration of multiple nonparenchymal cells including sinusoid endothelial cells. Vascular endothelial growth factor (VEGF) serves a crucial role in angiogenesis and liver regeneration. However, the lack of an high‑efficiency delivery system target to the injured site reduces the local therapeutic efficacy of VEGF. In our previous study, collagen binding VEGF (CBD‑VEGF) was established by fusing collagen binding domain (CBD) into the N‑terminal of native VEGF and improved cardiac function after myocardial infraction. The present study investigated the therapeutic effect of CBD‑VEGF on liver regeneration by a mouse model of partial hepatectomy. After injection through portal vein following 2/3 hepatectomy, CBD‑VEGF was largely retained in the hepatic extracellular matrix for 48 h. Furthermore, CBD‑VEGF application significantly promoted sinusoidal regeneration and remodeling in remanent liver tissue 48 h after hepatectomy. In addition, CBD‑VEGF treatment significantly enhanced the proliferation of hepatocytes at 2 and 3 days post‑surgery compared with native VEGF, concomitant with attenuated liver injury. In conclusion, these results demonstrated that CBD‑VEGF could be a promising therapeutic strategy for liver regeneration.
肝脏再生是一个复杂的过程,需要多种非实质细胞(包括窦内皮细胞)的协调。血管内皮生长因子(VEGF)在血管生成和肝脏再生中起着至关重要的作用。然而,由于缺乏高效的递送至损伤部位的靶向输送系统,降低了 VEGF 的局部治疗效果。在我们之前的研究中,通过将胶原结合结构域(CBD)融合到天然 VEGF 的 N 端,构建了胶原结合 VEGF(CBD-VEGF),并改善了心肌梗死后的心脏功能。本研究通过部分肝切除术的小鼠模型,探讨了 CBD-VEGF 对肝脏再生的治疗作用。在 2/3 肝切除术后通过门静脉注射后,CBD-VEGF 在肝外基质中可保留 48 小时。此外,CBD-VEGF 应用可显著促进肝切除后 48 小时残留肝组织中窦状隙的再生和重塑。此外,与天然 VEGF 相比,CBD-VEGF 治疗可显著增强术后 2 天和 3 天的肝细胞增殖,同时减轻肝损伤。总之,这些结果表明 CBD-VEGF 可能是一种有前途的肝脏再生治疗策略。