Gstm2-KO Mouse

Gstm2, glutathione S-transferase Mu 2, is a phase II detoxification and antioxidant enzyme. It is involved in multiple biological processes, such as regulating oxidative stress, mitochondrial oxidative phosphorylation, and MAPK pathways [1-4].

In various disease models, Gstm2 shows significant effects. In aged skin, its reduced expression disrupts skin homeostasis and wound repair, and EV-mediated delivery of Gstm2 mRNA can improve these conditions [1]. In prostate cancer, elevated GSTM2 confers resistance to SG-ARIs by rescuing cells from oxidative stress-associated damage and activating the p38 MAPK pathway [2]. In heart failure, GSTM2 overexpression relieves cardiac hypertrophy progression by attenuating DNA damage in cardiomyocytes [3]. In non-alcoholic steatohepatitis, GSTM2 deficiency aggravates the disease, as it suppresses ASK1 signaling [4]. In pancreatic cancer, down-regulation of GSTM2 enhances gemcitabine chemosensitivity [5].

Overall, Gstm2 is crucial in maintaining cellular homeostasis, especially in relation to oxidative stress and detoxification processes. Model-based research, especially in disease-relevant models like those of skin aging, prostate cancer, heart failure, non-alcoholic steatohepatitis, and pancreatic cancer, has revealed its key roles in disease development and potential as a therapeutic target.

References:

1. Wu, Haiyan, Yao, Zuochao, Li, Hongkun, Ding, Feixue, Zhu, Hongming. 2024. Improving dermal fibroblast-to-epidermis communications and aging wound repair through extracellular vesicle-mediated delivery of Gstm2 mRNA. In Journal of nanobiotechnology, 22, 307. doi:10.1186/s12951-024-02541-1. https://pubmed.ncbi.nlm.nih.gov/38825668/

2. Li, Chaohao, Liu, Jinpeng, He, Daheng, Wang, Chi, Liu, Xiaoqi. 2022. GSTM2 is a key molecular determinant of resistance to SG-ARIs. In Oncogene, 41, 4498-4511. doi:10.1038/s41388-022-02444-1. https://pubmed.ncbi.nlm.nih.gov/36038661/

3. Xu, Hongfei, Wang, Zhen, Wang, Yalin, Ni, Yiming, Li, Weidong. 2023. GSTM2 alleviates heart failure by inhibiting DNA damage in cardiomyocytes. In Cell & bioscience, 13, 220. doi:10.1186/s13578-023-01168-3. https://pubmed.ncbi.nlm.nih.gov/38037116/

4. Lan, Tian, Hu, Yufeng, Hu, Fengjiao, Rong, Xianglu, Guo, Jiao. 2021. Hepatocyte glutathione S-transferase mu 2 prevents non-alcoholic steatohepatitis by suppressing ASK1 signaling. In Journal of hepatology, 76, 407-419. doi:10.1016/j.jhep.2021.09.040. https://pubmed.ncbi.nlm.nih.gov/34656650/

5. Peng, Lisi, Zhuang, Lu, Lin, Kun, Ji, Baoan, Huang, Haojie. 2020. Downregulation of GSTM2 enhances gemcitabine chemosensitivity of pancreatic cancer in vitro and in vivo. In Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 21, 115-123. doi:10.1016/j.pan.2020.12.008. https://pubmed.ncbi.nlm.nih.gov/33341341/