LMO7, or LIM domain only 7, is a multifunctional protein involved in various biological processes. It acts as an E3 ubiquitin ligase in some contexts and is associated with pathways such as TGF-β signaling, glycolysis regulation, and is crucial for tissue development and homeostasis [1,2,4]. Genetic models, especially KO mouse models, have been instrumental in studying its functions.

In macrophages, LMO7 deficiency via metabolic-epigenetic reprogramming facilitates inflammatory injury. LMO7 degrades PFKFB3, an enzyme regulating glycolysis, inhibiting macrophage activation and attenuating murine colitis [1]. In vascular smooth muscle cells, global or SMC-specific LMO7 deletion in mice enhances neointimal formation, TGF-β signaling, and ECM deposition, suggesting LMO7 negatively regulates TGF-β-mediated fibrosis [2]. In pancreatic cancer, loss-of-function experiments showed that LMO7 defect suppresses cell proliferation, colony formation, and tumor growth and metastasis in vivo [3]. In pulmonary fibrosis, knockdown of LMO7 in mice impairs the profibrotic phenotype of fibroblasts, indicating its role in driving profibrotic fibroblast polarization [4]. In hepatocytes, LMO7 deficiency exacerbates diet-induced NASH progression, while its overexpression blocks hepatic lipid accumulation and inflammation [5]. In hair cells of Lmo7 KO mice, there are cuticular plate deficiencies leading to late-onset progressive hearing loss [6].

In summary, LMO7 is essential for maintaining normal physiological functions in multiple tissues. Through model-based research, especially KO mouse models, it has been revealed that LMO7 plays significant roles in inflammatory diseases like IBD, fibrotic diseases including pulmonary fibrosis, metabolic diseases such as NASH, cancer progression, and hearing function. Understanding LMO7's functions provides potential therapeutic targets for these diseases.

References:

1. Duan, Shixin, Lou, Xinyi, Chen, Shiyi, Sun, Lei, Qian, Feng. 2023. Macrophage LMO7 deficiency facilitates inflammatory injury via metabolic-epigenetic reprogramming. In Acta pharmaceutica Sinica. B, 13, 4785-4800. doi:10.1016/j.apsb.2023.09.012. https://pubmed.ncbi.nlm.nih.gov/38045056/

2. Xie, Yi, Ostriker, Allison C, Jin, Yu, Hwa, John, Martin, Kathleen A. . LMO7 Is a Negative Feedback Regulator of Transforming Growth Factor β Signaling and Fibrosis. In Circulation, 139, 679-693. doi:10.1161/CIRCULATIONAHA.118.034615. https://pubmed.ncbi.nlm.nih.gov/30586711/

3. Liu, Xinjian, Yuan, Hao, Zhou, Jing, Jiang, Kuirong, Li, Guangfu. 2021. LMO7 as an Unrecognized Factor Promoting Pancreatic Cancer Progression and Metastasis. In Frontiers in cell and developmental biology, 9, 647387. doi:10.3389/fcell.2021.647387. https://pubmed.ncbi.nlm.nih.gov/33763427/

4. Sun, Lei, Zhang, Hai-Bo, Jiang, Hong-Chao, Hu, Jian-Guo, Qian, Feng. 2025. LMO7 drives profibrotic fibroblast polarization and pulmonary fibrosis in mice through TGF-β signalling. In Acta pharmacologica Sinica, , . doi:10.1038/s41401-025-01488-9. https://pubmed.ncbi.nlm.nih.gov/40000880/

5. Wu, Tiangen, Chen, Xi, Xu, Kequan, Ma, Weijie, Yuan, Yufeng. 2023. LIM domain only 7 negatively controls nonalcoholic steatohepatitis in the setting of hyperlipidemia. In Hepatology (Baltimore, Md.), 79, 149-166. doi:10.1097/HEP.0000000000000585. https://pubmed.ncbi.nlm.nih.gov/37676481/

6. Du, Ting-Ting, Dewey, James B, Wagner, Elizabeth L, Kachar, Bechara, Shin, Jung-Bum. 2019. LMO7 deficiency reveals the significance of the cuticular plate for hearing function. In Nature communications, 10, 1117. doi:10.1038/s41467-019-09074-4. https://pubmed.ncbi.nlm.nih.gov/30850599/