Mapk8, also known as Mitogen-activated protein kinase 8, is involved in multiple cellular signaling pathways. It is a key component in the c-Jun N-terminal kinase (JNK) signaling pathway, which plays crucial roles in regulating cell proliferation, differentiation, apoptosis, and immune response [2,3,4]. Dysregulation of Mapk8 can lead to various diseases as it is associated with pathways like PI3K-Akt and MAPK signaling, which are important in cell survival and growth [5,6,7]. Genetic models such as gene knockout in mice can be valuable for studying its functions in vivo.

In intervertebral disc degeneration (IDD), Mapk8 was identified as a key biomarker. Analysis of gene expression profiles in IDD showed that Mapk8, along with other genes, was involved in autophagy-related pathways. In a rat IDD model, qPCR validation confirmed that Mapk8 was consistent with bioinformatic analysis results, suggesting it could be a potential therapeutic target for IDD [1]. In chicken male germ cell differentiation, knockdown/overexpression of Mapk8 affected the differentiation of embryonic stem cells into spermatogonial stem cells by inhibiting/activating the JNK signal [3]. In glioblastoma cells resistant to temozolomide, Mapk8 was up-regulated, and its inhibition restrained colony formation and induced apoptosis of these cells by suppressing the MAPK signaling pathway [6].

In conclusion, Mapk8 is essential in multiple biological processes and diseases. Through model-based research, especially in conditions like IDD, male germ cell differentiation, and glioblastoma, it has been shown to play significant roles. The study of Mapk8 in KO/CKO mouse models could further enhance our understanding of its functions and potentially lead to new therapeutic strategies for related diseases.

References:

1. Zhang, Yuxin, Zhang, Jiahui, Sun, Zhongyi, Xi, Xiaobing, Tian, Jiwei. 2023. MAPK8 and CAPN1 as potential biomarkers of intervertebral disc degeneration overlapping immune infiltration, autophagy, and ceRNA. In Frontiers in immunology, 14, 1188774. doi:10.3389/fimmu.2023.1188774. https://pubmed.ncbi.nlm.nih.gov/37325630/

2. Wang, Shuai, Deng, Zhantao, Ma, Yuanchen, Lyu, Feng-Juan, Zheng, Qiujian. 2020. The Role of Autophagy and Mitophagy in Bone Metabolic Disorders. In International journal of biological sciences, 16, 2675-2691. doi:10.7150/ijbs.46627. https://pubmed.ncbi.nlm.nih.gov/32792864/

3. Wang, Yingjie, Bi, Yulin, Zuo, Qisheng, Zhang, Ya-Ni, Li, Bichun. 2017. MAPK8 regulates chicken male germ cell differentiation through JNK signaling pathway. In Journal of cellular biochemistry, 119, 1548-1557. doi:10.1002/jcb.26314. https://pubmed.ncbi.nlm.nih.gov/28815778/

4. Li, Jian, Tian, Mouli, Hua, Tong, Zhang, Xiaoping, Yuan, Hongbin. 2021. Combination of autophagy and NFE2L2/NRF2 activation as a treatment approach for neuropathic pain. In Autophagy, 17, 4062-4082. doi:10.1080/15548627.2021.1900498. https://pubmed.ncbi.nlm.nih.gov/33834930/

5. Aihaiti, Yirixiati, Song Cai, Yong, Tuerhong, Xiadiye, Xu, Ke, Xu, Peng. 2021. Therapeutic Effects of Naringin in Rheumatoid Arthritis: Network Pharmacology and Experimental Validation. In Frontiers in pharmacology, 12, 672054. doi:10.3389/fphar.2021.672054. https://pubmed.ncbi.nlm.nih.gov/34054546/

6. Xu, Peng, Zhang, Guofeng, Hou, Shuangxing, Sha, Long-Gui. 2018. MAPK8 mediates resistance to temozolomide and apoptosis of glioblastoma cells through MAPK signaling pathway. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 106, 1419-1427. doi:10.1016/j.biopha.2018.06.084. https://pubmed.ncbi.nlm.nih.gov/30119215/

7. Ge, Bingjie, Yan, Kexin, Sang, Rui, Qiu, Qian, Zhang, Xuemei. 2024. Integrated network toxicology, molecular docking, and in vivo experiments to elucidate molecular mechanism of aflatoxin B1 hepatotoxicity. In Ecotoxicology and environmental safety, 275, 116278. doi:10.1016/j.ecoenv.2024.116278. https://pubmed.ncbi.nlm.nih.gov/38564860/