Mep1a, encoding meprin 1α metalloendopeptidase, is a zinc metalloprotease. It is involved in regulating various biological processes, with its functions including participation in the regulation of inflammatory response, fibrosis, and extracellular matrix protein regulation. It has been associated with multiple disease-related pathways [1-6]. Genetic models, especially gene knockout mouse models, have been crucial in studying its functions.

In gene knockout mouse models, Mep1a deficiency significantly alleviated TAC-and Ang II-induced cardiac remodeling and dysfunction, reducing cardiac hypertrophy, fibrosis, and inflammation [1]. In atherosclerosis, Mep1a-/-Apoe-/-mice showed reduced atherosclerotic lesion sizes, decreased necrosis, and changes in immune cell contents and oxidative stress markers [2]. For abdominal aortic aneurysms, Mep1A deficiency in mice decreased AAA formation, elastic lamina degradation, and SMC apoptosis [3]. In IBD, Mep1a knockout mice had more severe intestinal injury and inflammation [4].

In conclusion, Mep1a plays essential roles in processes like cardiac remodeling, atherosclerosis, abdominal aortic aneurysms, and intestinal inflammation. Gene knockout mouse models have been instrumental in revealing these roles, highlighting Mep1a as a potential therapeutic target in related disease areas such as heart failure, atherosclerosis, and abdominal aortic aneurysms.

References:

1. Ge, Weipeng, Hou, Cuiliu, Zhang, Wei, Zhao, Hongmei, Wang, Jing. 2020. Mep1a contributes to Ang II-induced cardiac remodeling by promoting cardiac hypertrophy, fibrosis and inflammation. In Journal of molecular and cellular cardiology, 152, 52-68. doi:10.1016/j.yjmcc.2020.11.015. https://pubmed.ncbi.nlm.nih.gov/33301800/

2. Grainger, Andrew T, Pilar, Nathanael, Li, Jun, Becker-Pauly, Christoph, Shi, Weibin. . Identification of Mep1a as a susceptibility gene for atherosclerosis in mice. In Genetics, 219, . doi:10.1093/genetics/iyab160. https://pubmed.ncbi.nlm.nih.gov/34849841/

3. Gao, Ran, Liu, Duan, Guo, Wenjun, Zheng, Yuehong, Wang, Jing. 2020. Meprin-α (Mep1A) enhances TNF-α secretion by mast cells and aggravates abdominal aortic aneurysms. In British journal of pharmacology, 177, 2872-2885. doi:10.1111/bph.15019. https://pubmed.ncbi.nlm.nih.gov/32072633/

4. Banerjee, S, Oneda, B, Yap, L M, Lottaz, D, Bond, J S. 2009. MEP1A allele for meprin A metalloprotease is a susceptibility gene for inflammatory bowel disease. In Mucosal immunology, 2, 220-31. doi:10.1038/mi.2009.3. https://pubmed.ncbi.nlm.nih.gov/19262505/