Lgmn-KO Mouse

Lgmn, also known as legumain, is an in vivo-active cysteine protease that catalyzes the degradation of numerous proteins. It is involved in multiple biological processes and is linked to various disease-related pathways, such as those in the tumor microenvironment, cardiac repair, and vascular biology [1,2,3]. Genetic models, like knockout (KO) and conditional knockout (CKO) mouse models, have been crucial in understanding its functions.

In KO mouse models, Lgmn deficiency led to exacerbation of cardiac function after myocardial infarction, with accumulation of apoptotic cardiomyocytes, reduced in vivo efferocytosis, and defective intracellular calcium mobilization, indicating its role in cardiac repair [2]. In thoracic aortic dissection (TAD) models, Lgmn-deficient or inhibited mice showed ameliorated TAD progression, as macrophage-derived LGMN was found to bind to integrin αvβ3 in vascular smooth muscle cells (VSMCs), affecting VSMC differentiation and extracellular matrix degradation [3]. Also, CD4+ T-cell-specific Lgmn-knockout mice had reduced hypertension-induced damage, as LGMN in T cells was shown to impair regulatory T cell (Treg) differentiation and function by degrading TRAF6 [4].

In conclusion, Lgmn plays essential roles in cardiac repair, vascular biology, and T-cell-mediated immune responses related to hypertension. The use of Lgmn KO/CKO mouse models has significantly contributed to understanding its functions in these disease areas, providing potential therapeutic targets for myocardial infarction, TAD, and hypertension.

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. He, Yuhu, Zou, Pu, Lu, Junmi, Liu, Qiming, Zhou, Shenghua. 2023. CD4+ T-Cell Legumain Deficiency Attenuates Hypertensive Damage via Preservation of TRAF6. In Circulation research, 134, 9-29. doi:10.1161/CIRCRESAHA.123.322835. https://pubmed.ncbi.nlm.nih.gov/38047378/