Nostrin, also known as nitric oxide synthase traffic inducer, is a pleiotropic regulator involved in modulating endothelial cell function and signaling. It interacts with endothelial nitric oxide synthase (eNOS), affecting its subcellular distribution and NO release, thus participating in the eNOS-NO pathway [1,4,5]. It also has a role in many biological processes like trophoblast differentiation, vascular development, and is associated with various diseases [2,6]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In cirrhosis and acute-on-chronic liver failure (ACLF) models, CCl4-treated mice showed elevated hepatic Nostrin expression and reduced peNOS (an indicator of eNOS activity), and LPS challenge further exacerbated these changes. Nostrin knockdown in human umbilical vein endothelial cells (HUVECs) improved peNOS expression, NO synthesis, and reduced inflammation. This indicates a role for the Nostrin-eNOS-NO pathway in cirrhosis and ACLF development [1]. In benign prostatic hyperplasia (BPH), NOSTRIN expression was inhibited in mouse and cell models. Overexpression of NOSTRIN in prostate epithelial cells inhibited cell proliferation, oxidative stress, and inflammation, likely through the inhibition of NF-κB signaling [3].

In conclusion, Nostrin plays essential roles in multiple biological processes and diseases. Model-based research, especially KO/CKO mouse models, has revealed its functions in conditions like cirrhosis, ACLF, and BPH. Understanding Nostrin can provide new insights into the mechanisms of these diseases and potential therapeutic targets.