Cth-KO Mouse

Cth, also known as cystathionine gamma-lyase (CSE), is one of the main hydrogen sulfide (H2S) producing enzymes. It is involved in the transsulfuration pathway, converting cystathionine to cysteine. H2S, produced by Cth, has various functions in biological processes such as inflammation regulation, cardiovascular function, and cell proliferation [1,2,3,4,6,7]. Genetic models, like knockout mice, are valuable for studying Cth's role.

In a GBM in vivo model, genetic ablation of Cth in C57BL/6J WT mice led to reduced tumor volume and the stemness transcription factor SOX2, suggesting Cth promotes glioblastoma formation [1]. In cardiovascular studies, Cth/MPST double knockout mice showed enhanced vasorelaxation, reduced blood pressure, and upregulated eNOS/sGC pathway, indicating Cth's role in blood pressure regulation [4]. In the context of intestinal ischaemia‒reperfusion injury, Cth in macrophages activated the ERK1/2 signalling pathway, induced efferocytosis, and promoted intestinal barrier repair [5]. Deletion of Cth in VSMCs exacerbated plaque vulnerability in atherosclerotic studies, as Cth-H2S increases VSMC autophagy, promotes collagen secretion, and inhibits apoptosis [7].

In conclusion, Cth plays essential roles in multiple biological processes. Through gene knockout mouse models, its functions in glioblastoma development, cardiovascular homeostasis, intestinal barrier repair, and atherosclerotic plaque stability have been revealed. These findings contribute to understanding the mechanisms of related diseases and may provide potential therapeutic targets.

References:

1. Peleli, Maria, Antoniadou, Ivi, Rodrigues-Junior, Dorival Mendes, Moustakas, Aristidis, Papapetropoulos, Andreas. 2023. Cystathionine gamma-lyase (CTH) inhibition attenuates glioblastoma formation. In Redox biology, 64, 102773. doi:10.1016/j.redox.2023.102773. https://pubmed.ncbi.nlm.nih.gov/37300955/

2. Lin, Ting, Bai, Xu, Gao, Yuan, Zhang, Quanwei, Zhao, Xingxu. 2022. CTH/H2S Regulates LPS-Induced Inflammation through IL-8 Signaling in MAC-T Cells. In International journal of molecular sciences, 23, . doi:10.3390/ijms231911822. https://pubmed.ncbi.nlm.nih.gov/36233122/

3. Söderström, Elisabet, Andersson, Jonas, Söderberg, Stefan, Nilsson, Torbjörn K, Hultdin, Johan. 2022. CTH G1208T and MTHFR A1298C polymorphisms are associated with a higher risk of a first myocardial infarction with fatal outcome among women. In Drug metabolism and personalized therapy, 38, 57-63. doi:10.1515/dmpt-2022-0119. https://pubmed.ncbi.nlm.nih.gov/36279151/

4. Katsouda, Antonia, Markou, Maria, Zampas, Paraskevas, Bucci, Mariarosaria, Papapetropoulos, Andreas. 2023. CTH/MPST double ablation results in enhanced vasorelaxation and reduced blood pressure via upregulation of the eNOS/sGC pathway. In Frontiers in pharmacology, 14, 1090654. doi:10.3389/fphar.2023.1090654. https://pubmed.ncbi.nlm.nih.gov/36860295/

5. Zhao, Xiao-Hu, Yang, Ting, Zheng, Meng-Yao, Zhang, Peng-Cheng, Sun, Da-Li. 2023. Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair. In Cell communication and signaling : CCS, 21, 17. doi:10.1186/s12964-022-01030-y. https://pubmed.ncbi.nlm.nih.gov/36691021/

6. Román, Gustavo C, Mancera-Páez, Oscar, Bernal, Camilo. 2019. Epigenetic Factors in Late-Onset Alzheimer's Disease: MTHFR and CTH Gene Polymorphisms, Metabolic Transsulfuration and Methylation Pathways, and B Vitamins. In International journal of molecular sciences, 20, . doi:10.3390/ijms20020319. https://pubmed.ncbi.nlm.nih.gov/30646578/

7. Chen, Zhenzhen, Ouyang, Chenxi, Zhang, Haizeng, Cai, Jun, Geng, Bin. 2022. Vascular smooth muscle cell-derived hydrogen sulfide promotes atherosclerotic plaque stability via TFEB (transcription factor EB)-mediated autophagy. In Autophagy, 18, 2270-2287. doi:10.1080/15548627.2022.2026097. https://pubmed.ncbi.nlm.nih.gov/35090378/