Polyethylenimine Triggers Dll4 Degradation to Regulate Angiogenesis In Vitro.
Binghua ChengYanyan LiYa-Bin JiWenli ShiMeiqing LiJiwei ZhengLi DingKe LiuLijing FangYe XuHongchang LiXiming ShaoPublished in: ACS omega (2024)
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.
Keyphrases
- endothelial cells
- vascular endothelial growth factor
- high glucose
- cell proliferation
- signaling pathway
- nucleic acid
- cell surface
- gene expression
- epithelial mesenchymal transition
- squamous cell carcinoma
- pi k akt
- cancer therapy
- drug delivery
- oxidative stress
- combination therapy
- dna methylation
- endoplasmic reticulum stress
- induced apoptosis
- lymph node metastasis
- tissue engineering