Dusp1, also known as dual-specificity phosphatase 1, is a key regulator involved in multiple biological processes. It plays a vital role in maintaining mitochondrial function and structural integrity, and is associated with pathways such as MAPK, cGAS-STING, and JAK2/STAT3 [1,4,5]. Genetic models, like Dusp1 knockout mice, are valuable tools for studying its functions.

In a mouse model of ischemic acute kidney injury, Dusp1 gene deletion exacerbated acute ischemic injury, post-ischemic renal fibrosis, and tubular mitochondrial dysfunction. Mechanistically, DUSP1 deficiency led to aberrant phosphorylation of JNK and BAX mitochondria translocation, promoting mtDNA leakage and activation of the cGAS-STING pathway [1]. In acute myeloid leukemia, DUSP1 knockdown by siRNA sensitized AML cells to cytarabine treatments, and its expression levels were correlated with patient outcomes [2]. In gouty arthritis, downregulation of DUSP1 in THP-1 monocytes increased the secretion of inflammatory cytokines after MSU treatment [3].

In conclusion, Dusp1 plays essential roles in maintaining mitochondrial integrity, regulating cell responses to drugs in leukemia, and modulating the immune response in gouty arthritis. The use of Dusp1 knockout mouse models has provided significant insights into its functions in these disease areas, helping to understand the underlying molecular mechanisms and potentially identify new therapeutic targets.

References:

1. Shi, Lang, Zha, Hongchu, Pan, Zhou, Song, Zhixia, Zhu, Jiefu. 2023. DUSP1 protects against ischemic acute kidney injury through stabilizing mtDNA via interaction with JNK. In Cell death & disease, 14, 724. doi:10.1038/s41419-023-06247-4. https://pubmed.ncbi.nlm.nih.gov/37935658/

2. Sun, Huali, Ren, Yanling, Zhou, Xinping, Ying, Shenpeng, Lin, Peipei. . DUSP1 Signaling Pathway Regulates Cytarabine Sensitivity in Acute Myeloid Leukemia. In Technology in cancer research & treatment, 22, 15330338231207765. doi:10.1177/15330338231207765. https://pubmed.ncbi.nlm.nih.gov/37872685/

3. Nie, Jing, Qiu, Hongbin. . DUSP1 Mitigates MSU-Induced Immune Response in Gouty Arthritis Reinforcing Autophagy. In Frontiers in bioscience (Landmark edition), 29, 222. doi:10.31083/j.fbl2906222. https://pubmed.ncbi.nlm.nih.gov/38940057/

4. Sheng, Junqin, Li, Hongyan, Dai, Qin, Zhang, Jisheng, Feng, Jianxun. 2018. DUSP1 recuses diabetic nephropathy via repressing JNK-Mff-mitochondrial fission pathways. In Journal of cellular physiology, 234, 3043-3057. doi:10.1002/jcp.27124. https://pubmed.ncbi.nlm.nih.gov/30191967/

5. Wang, Ying, Wang, Hua-Min, Zhou, Yan, Hu, Peng, Chen, Liang-Biao. . Dusp1 regulates thermal tolerance limits in zebrafish by maintaining mitochondrial integrity. In Zoological research, 44, 126-141. doi:10.24272/j.issn.2095-8137.2022.397. https://pubmed.ncbi.nlm.nih.gov/36419379/