posted on 2024-02-07, 19:33authored byBinghua Cheng, Yanyan Li, Ya-Bin Ji, Wenli Shi, Meiqing Li, Jiwei Zheng, Li Ding, Ke Liu, Lijing Fang, Ye Xu, Hongchang Li, Ximing Shao
The Dll4-Notch signaling
pathway plays a crucial role in the regulation
of angiogenesis and is a promising therapeutic target for diseases
associated with abnormal angiogenesis, such as cancer and ophthalmic
diseases. Here, we find that polyethylenimine (PEI), a cationic polymer
widely used as nucleic acid transfection reagents, can target the
Notch ligand Dll4. By immunostaining and immunoblotting, we demonstrate
that PEI significantly induces the clearance of cell–surface
Dll4 and facilitates its degradation through the lysosomal pathway.
As a result, the activation of Notch signaling in endothelial cells
is effectively inhibited by PEI, as evidenced by the observed decrease
in the generation of the activated form of Notch and expression of
Notch target genes Hes1 and Hey1. Furthermore, through blocking Dll4-mediated
Notch signaling, PEI treatment enhances angiogenesis in vitro. Together,
our study reveals a novel biological effect of PEI and establishes
a foundation for the development of a Dll4-targeted biomaterial for
the treatment of angiogenesis-related disease.