Collagen‑binding vascular endothelial growth factor (CBD‑VEGF) promotes liver regeneration in murine partial hepatectomy
Susu Wei, Zhichao Li, Qiangqiang Shi, Xiaoyu Luan, Xinying Yuan, Yaxin Li, Chuanlong Guo, Xianggen Wu, Chunying Shi, Guohu Di
Abstract
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.