Serpina3n, a secretory serine protease inhibitor belonging to clade "a", plays significant roles in multiple biological processes. It is involved in pathways such as the complement cascade, apoptosis, and wound healing, and has been associated with various diseases including those in the central nervous system (CNS) [1]. Its human orthologue is SERPINA3 (α1-antichymotrypsin). Genetic models, like KO/CKO mouse models, are crucial for studying its functions.

In a Serpina3n conditional knockout mice model, genetic deletion led to increased activity of substrate proteases, poorly compacted matrix, and worse post-infarct cardiac function after myocardial infarction. There was also increased inflammation, adverse myocyte hypertrophy, and expression of pro-hypertrophic genes, indicating its role in regulating cardiac remodelling [3]. In a mouse model of chemically induced colitis, genetic ablation of Serpina3n delayed the resolution of induced inflammation, showing its role in the resolution of inflammation [2]. In male mice with hepatocyte Serpina3N knockout, hepatic deletion attenuated steatosis, altered lipid metabolism genes, increased fatty acid oxidation activity, and enhanced insulin signaling, suggesting its role in regulating non-alcoholic fatty liver disease (NAFLD) and glucose homeostasis [4].

In conclusion, Serpina3n is essential in processes like inflammation resolution, cardiac remodelling, and regulation of NAFLD and glucose homeostasis. The KO/CKO mouse models have provided valuable insights into its role in these disease areas, contributing to a better understanding of the underlying mechanisms and potentially leading to new therapeutic strategies.

References:

1. Aslam, Mehwish Saba, Yuan, Liudi. 2019. Serpina3n: Potential drug and challenges, mini review. In Journal of drug targeting, 28, 368-378. doi:10.1080/1061186X.2019.1693576. https://pubmed.ncbi.nlm.nih.gov/31790278/

2. Ho, Yen-Ting, Shimbo, Takashi, Wijaya, Edward, Kaneda, Yasufumi, Tamai, Katsuto. 2021. Longitudinal Single-Cell Transcriptomics Reveals a Role for Serpina3n-Mediated Resolution of Inflammation in a Mouse Colitis Model. In Cellular and molecular gastroenterology and hepatology, 12, 547-566. doi:10.1016/j.jcmgh.2021.04.004. https://pubmed.ncbi.nlm.nih.gov/33862275/

3. Sun, Qihao, Chen, Wei, Wu, Rimao, Li, Shen, Deb, Arjun. . Serine protease inhibitor, SerpinA3n, regulates cardiac remodelling after myocardial infarction. In Cardiovascular research, 120, 943-953. doi:10.1093/cvr/cvae075. https://pubmed.ncbi.nlm.nih.gov/38666458/

4. Tran, Melanie, Mostofa, Golam, Picard, Michael, Wang, Li, Shin, Dong-Ju. 2023. SerpinA3N deficiency attenuates steatosis and enhances insulin signaling in male mice. In The Journal of endocrinology, 256, . doi:10.1530/JOE-22-0073. https://pubmed.ncbi.nlm.nih.gov/36625462/