Arg2, or arginase 2, is a key hydrolase in the urea cycle, hydrolyzing L-arginine to urea and L-ornithine. It is involved in multiple biological processes, including fatty acid oxidation, cell cycle regulation, and mitochondrial function. It has been associated with pathways such as the STAT3, NF-κB, and Wnt/β -catenin signaling cascades, and is of great biological importance in various diseases [3]. Genetic models, like gene knockout (KO) and conditional knockout (CKO) mouse models, have been crucial in studying its function.

In non-alcoholic steatohepatitis (NASH), conditional knockout of Spp1 in myeloid cells worsened NASH, while conditional knockin of Spp1 induced Arg2, enhancing fatty acid oxidation in hepatocytes, thus protecting from NASH. The induction of Arg2 stemmed from enhanced production of oncostatin-M in macrophages, which activated STAT3 signaling [1]. In adenomyosis, Arg2 knockdown promoted G0/G1 cell cycle arrest, mitochondrial dysfunction, and apoptosis via regulation of NF-κB and Wnt/β -catenin signaling cascades [2]. In contrast-induced acute kidney injury, ARG2 knockout mice showed ameliorated kidney dysfunction, tubular injury, decreased nitrosative stress and apoptosis, indicating that ARG2 plays a crucial role in this condition [4].

In conclusion, Arg2 is essential in processes like fatty acid oxidation, cell cycle regulation, and mitochondrial function as revealed through model-based research. KO/CKO mouse models have significantly contributed to understanding its role in diseases such as NASH, adenomyosis, and contrast-induced acute kidney injury, providing potential therapeutic targets for these conditions.

References:

1. Han, Hui, Ge, Xiaodong, Komakula, Sai Santosh Babu, Guzman, Grace, Nieto, Natalia. 2023. Macrophage-derived Osteopontin (SPP1) Protects From Nonalcoholic Steatohepatitis. In Gastroenterology, 165, 201-217. doi:10.1053/j.gastro.2023.03.228. https://pubmed.ncbi.nlm.nih.gov/37028770/

2. Xu, Yaping, Shao, Lin, Zhou, Zhan, Wanyan, Wenya, Yuan, Yinping. 2024. ARG2 knockdown promotes G0/G1 cell cycle arrest and mitochondrial dysfunction in adenomyosis via regulation NF-κB and Wnt/Β-catenin signaling cascades. In International immunopharmacology, 140, 112817. doi:10.1016/j.intimp.2024.112817. https://pubmed.ncbi.nlm.nih.gov/39116499/

3. Niu, Fanglin, Yu, Yi, Li, Zhuozhuo, Qian, Lu, Xiong, Yuyan. 2022. Arginase: An emerging and promising therapeutic target for cancer treatment. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 149, 112840. doi:10.1016/j.biopha.2022.112840. https://pubmed.ncbi.nlm.nih.gov/35316752/

4. Zhou, Ling-Yun, Liu, Kun, Yin, Wen-Jun, Wu, Yi-Feng, Zuo, Xiao-Cong. 2023. Arginase2 mediates contrast-induced acute kidney injury via facilitating nitrosative stress in tubular cells. In Redox biology, 67, 102929. doi:10.1016/j.redox.2023.102929. https://pubmed.ncbi.nlm.nih.gov/37856999/