Loxl4, lysyl oxidase-like 4, is a copper and lysine tyrosylquinone-dependent amine oxidase and a member of the lysyl oxidase family. It catalyzes the cross-linking of elastin and collagen in the extracellular matrix, playing a key role in extracellular matrix (ECM) formation and repair [1,4]. The ECM is crucial for tissue structure and function, and thus Loxl4 is of great biological importance. Gene knockout (KO) mouse models can be valuable for studying Loxl4's function.

In lung fibrosis, genetic ablation of Loxl4 markedly disrupts pathological collagen cross-linking and fibrosis, while Loxl2 ablation only leads to a modest reduction. Moreover, knockout of both Loxl2 and Loxl4 offers no additive antifibrotic effects compared to Loxl4 deletion alone, as Loxl4 deficiency decreases the expression of other LOX family members including Loxl2. This indicates that Loxl4 is the main LOX activity underlying pathological collagen cross-linking and lung fibrosis [2]. In contrast, in angiotensin II-induced aortic aneurysm mouse models, abrogation of Loxl4 did not induce a more severe thoracic or abdominal aortic aneurysm compared with wild-type mice, suggesting Loxl4 may not play a major role in this disease [3].

In conclusion, Loxl4 is essential for extracellular matrix cross-linking, especially in relation to collagen. Mouse KO models have revealed its significant role in lung fibrosis, highlighting its potential as a target for anti-fibrotic therapies. However, it seems to have a negligible role in angiotensin II-induced aortic aneurysm development. These findings contribute to our understanding of the biological functions of Loxl4 in different disease contexts.

References:

1. Wang, Jiaming, Chen, Chaojian, Huang, Jiayi, Li, Enmin, Zou, Haiying. 2023. The possibilities of LOXL4 as a prognostic marker for carcinomas. In Amino acids, 55, 1519-1529. doi:10.1007/s00726-023-03343-9. https://pubmed.ncbi.nlm.nih.gov/37814029/

2. Ma, Hsiao-Yen, Li, Qingling, Wong, Weng Ruh, Sandoval, Wendy, Ding, Ning. 2023. LOXL4, but not LOXL2, is the critical determinant of pathological collagen cross-linking and fibrosis in the lung. In Science advances, 9, eadf0133. doi:10.1126/sciadv.adf0133. https://pubmed.ncbi.nlm.nih.gov/37235663/

3. Li, Huimin, Guo, Jun, Jia, Yiting, Kong, Wei, Li, Wei. 2021. LOXL4 Abrogation Does Not Exaggerate Angiotensin II-Induced Thoracic or Abdominal Aortic Aneurysm in Mice. In Genes, 12, . doi:10.3390/genes12040513. https://pubmed.ncbi.nlm.nih.gov/33807332/

4. Liu, Ruai, Li, Bin, Zi, Jiaji, Pu, Yuanqian, Xiong, Wei. 2024. The dual role of LOXL4 in the pathogenesis and development of human malignant tumors: a narrative review. In Translational cancer research, 13, 2026-2042. doi:10.21037/tcr-23-2003. https://pubmed.ncbi.nlm.nih.gov/38737700/