Ctss, also known as Cathepsin S, is a member of the lysosomal cysteine cathepsin family of proteases. It has a normal restricted expression profile but can be inducibly upregulated. Functionally, it degrades unwanted and damaged proteins within the lysosome, and also mediates antigen processing and presentation, and cleaves substrates both intra-and extracellularly. It is involved in multiple biological pathways relevant to various physiological and pathological conditions [1].

In a mouse FeCl3 model, CTSS-deficient mice (CTSS-/-) showed decreased levels of inflammatory and pro-thrombotic factors and increased levels of protective factors compared to wild-type mice under stress, indicating CTSS plays a role in stress-related thrombosis [2]. In liver fibrosis mouse models, genetic ablation of Ctss remarkably suppressed liver fibrogenesis, suggesting it is a profibrotic factor [3]. In a peripheral nerve injury model in rats, pharmacological inhibition or genetic silencing of CTSS at the injured site delayed sensory recovery, highlighting its role in axon regeneration [4].

In conclusion, Ctss is a multifunctional protease involved in diverse biological processes. The use of gene knockout (KO) and conditional knockout (CKO) mouse models, as well as other loss-of-function experiments, has revealed its significance in diseases such as thrombosis, liver fibrosis, and in processes like peripheral nerve regeneration, providing potential therapeutic targets for these conditions.

References:

1. Smyth, Peter, Sasiwachirangkul, Jutharat, Williams, Rich, Scott, Christopher J. 2022. Cathepsin S (CTSS) activity in health and disease - A treasure trove of untapped clinical potential. In Molecular aspects of medicine, 88, 101106. doi:10.1016/j.mam.2022.101106. https://pubmed.ncbi.nlm.nih.gov/35868042/

2. Xu, Shengnan, Piao, Limei, Wan, Ying, Kuzuya, Masafumi, Cheng, Xian Wu. 2023. CTSS Modulates Stress-Related Carotid Artery Thrombosis in a Mouse FeCl3 Model. In Arteriosclerosis, thrombosis, and vascular biology, 43, e238-e253. doi:10.1161/ATVBAHA.122.318455. https://pubmed.ncbi.nlm.nih.gov/37128920/

3. Zuo, Tao, Xie, Qi, Liu, Jinfang, Lu, Shichun, Xu, Ping. 2023. Macrophage-Derived Cathepsin S Remodels the Extracellular Matrix to Promote Liver Fibrogenesis. In Gastroenterology, 165, 746-761.e16. doi:10.1053/j.gastro.2023.05.039. https://pubmed.ncbi.nlm.nih.gov/37263311/

4. Oshima, Eri, Hayashi, Yoshinori, Xie, Zhen, Shirota, Tatsuo, Shinoda, Masamichi. 2023. M2 macrophage-derived cathepsin S promotes peripheral nerve regeneration via fibroblast-Schwann cell-signaling relay. In Journal of neuroinflammation, 20, 258. doi:10.1186/s12974-023-02943-2. https://pubmed.ncbi.nlm.nih.gov/37946211/