Notch3 is a gene encoding a receptor in the Notch signaling pathway, which is highly conserved and involved in cell-cell interaction, embryogenesis, and tissue commitment [3]. Notch3 is expressed almost exclusively in vascular smooth muscle cells (VSMCs), where it plays a crucial role in vascular development and differentiation, and is involved in regulating VSMC switching between contractile and synthetic phenotypes under pathological conditions [2].

Notch3 mutations have been identified as the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common hereditary cerebral small vessel disease [1,5,6]. In bladder cancer, NOTCH3 is significantly upregulated, and its knockdown inhibits cell proliferation, migration, invasion, as well as tumor growth and metastasis in vivo, suggesting it promotes the malignant progression of bladder cancer [4].

In conclusion, Notch3 is essential for vascular development and differentiation, especially in VSMCs. Studies, including those on CADASIL and bladder cancer, have revealed its importance in disease-related biological processes. Research on Notch3, especially through in vivo models, helps to understand the molecular mechanisms of related diseases, providing potential targets for treatment and prevention.