Lum-KO Mouse

Lum, also known as lumican, is a member of the small leucine-rich proteoglycan family. It is involved in multiple biological processes and pathways. For instance, it plays roles in extracellular matrix-related pathways, and is associated with cell proliferation regulation and the inflammatory response [2,3,4].

In calcific aortic valve disease (CAVD), single-cell RNA-sequencing delineated the VIC osteogenic transformation process and highlighted LUM as a novel key regulator. In vitro, ex vivo, in vivo experiments and double knockout (ApoE -/-//LUM -/-) mice showed that LUM promotes valve calcification via activation of inflammatory pathways, augmentation of cellular glycolysis, and induction of histone lactylation (H3K14la and H3K9la), which is associated with the expression of calcific genes Runx2 and BMP2 [1].

In gastric cancer, high LUM expression is correlated with poor tumor differentiation, advanced T stage and pathological stage, and predicts a poor prognosis. It may act as an oncogene in gastric cancer progression [2,3]. Also, LUM was identified as the hub gene of advanced fibrosis in non-alcoholic fatty liver disease patients [4].

In conclusion, LUM has diverse essential biological functions, especially in extracellular matrix-related processes. The use of gene knockout mouse models, like in the study of CAVD, has significantly contributed to understanding its role in specific disease conditions such as CAVD, gastric cancer, and non-alcoholic fatty liver disease, providing potential therapeutic targets for these diseases.

References:

1. Huang, Yuming, Wang, Chunli, Zhou, Tingwen, Dong, Nianguo, Xu, Kang. . Lumican promotes calcific aortic valve disease through H3 histone lactylation. In European heart journal, 45, 3871-3885. doi:10.1093/eurheartj/ehae407. https://pubmed.ncbi.nlm.nih.gov/38976370/

2. Chen, Xiaowei, Li, Xin, Hu, Xueju, Wei, Pingmin, Shen, Xiaobing. 2020. LUM Expression and Its Prognostic Significance in Gastric Cancer. In Frontiers in oncology, 10, 605. doi:10.3389/fonc.2020.00605. https://pubmed.ncbi.nlm.nih.gov/32500021/

3. Xu, Wu, Chen, Shasha, Jiang, Qiuju, Ruan, Caishun, Shi, Bin. 2023. LUM as a novel prognostic marker and its correlation with immune infiltration in gastric cancer: a study based on immunohistochemical analysis and bioinformatics. In BMC gastroenterology, 23, 455. doi:10.1186/s12876-023-03075-w. https://pubmed.ncbi.nlm.nih.gov/38129820/

4. Chang, Yue, He, Jiange, Xiang, Xiaohui, Li, Hai. 2020. LUM is the hub gene of advanced fibrosis in nonalcoholic fatty liver disease patients. In Clinics and research in hepatology and gastroenterology, 45, 101435. doi:10.1016/j.clinre.2020.04.006. https://pubmed.ncbi.nlm.nih.gov/32386798/