Lgmn-KO Mouse

Lgmn, also known as legumain, is an in vivo-active cysteine protease. It catalyzes the degradation of numerous proteins and is involved in multiple biological processes. Its functions include influencing the tumor microenvironment, cardiac repair, and extracellular matrix degradation, and it is associated with pathways such as those related to hypoxia-inducible factor 1-alpha (HIF1α) signaling, GSK-3β-STAT3 signaling, and chaperone-mediated autophagy. Genetic models, like knockout mice, have been crucial in studying its functions [1,2,3].

In multiple knockout and conditional knockout mouse models, Lgmn deficiency has shown various impacts. In myocardial infarction, Lgmn-deficient mice had exacerbated cardiac function, apoptotic cardiomyocyte accumulation, and reduced in vivo efferocytosis, highlighting its role in cardiac repair [2]. In thoracic aortic dissection (TAD), Lgmn-deficient or inhibited mice had ameliorated BAPN-induced TAD progression, indicating its role in VSMC phenotype transformation and TAD development [3]. In acute kidney injury (AKI), Lgmn-deficient mice had attenuated acute tubular injury, inflammation, and ferroptosis, suggesting its role in promoting tubular ferroptosis [4].

In conclusion, Lgmn is essential in processes such as cardiac repair, TAD development, and AKI-related tubular ferroptosis. Gene knockout and conditional knockout mouse models have significantly contributed to understanding Lgmn's role in these disease areas, providing potential therapeutic targets for myocardial infarction, TAD, and AKI [2,3,4].

References:

1. Khan, Safir Ullah, Khan, Ibrar Muhammad, Khan, Munir Ullah, Khan, Nazir Muhammad, Liu, Yong. 2023. Role of LGMN in tumor development and its progression and connection with the tumor microenvironment. In Frontiers in molecular biosciences, 10, 1121964. doi:10.3389/fmolb.2023.1121964. https://pubmed.ncbi.nlm.nih.gov/36825203/

2. Jia, Daile, Chen, Siqin, Bai, Peiyuan, Sun, Aijun, Ge, Junbo. 2022. Cardiac Resident Macrophage-Derived Legumain Improves Cardiac Repair by Promoting Clearance and Degradation of Apoptotic Cardiomyocytes After Myocardial Infarction. In Circulation, 145, 1542-1556. doi:10.1161/CIRCULATIONAHA.121.057549. https://pubmed.ncbi.nlm.nih.gov/35430895/

3. Pan, Lihong, Bai, Peiyuan, Weng, Xinyu, Sun, Aijun, Ge, Junbo. 2022. Legumain Is an Endogenous Modulator of Integrin αvβ3 Triggering Vascular Degeneration, Dissection, and Rupture. In Circulation, 145, 659-674. doi:10.1161/CIRCULATIONAHA.121.056640. https://pubmed.ncbi.nlm.nih.gov/35100526/

4. Chen, Chuan'ai, Wang, Dekun, Yu, Yangyang, Yue, Shijing, Tan, Xiaoyue. 2021. Legumain promotes tubular ferroptosis by facilitating chaperone-mediated autophagy of GPX4 in AKI. In Cell death & disease, 12, 65. doi:10.1038/s41419-020-03362-4. https://pubmed.ncbi.nlm.nih.gov/33431801/