CRLF1, short for cytokine receptor-like factor-1, is a soluble type I cytokine receptor. It functions in regulating various biological processes such as cell growth, differentiation, and immune function by interacting with cytokines like CLCF1 (cardiotrophin-like cytokine factor 1), triggering intracellular signalling cascades [1].

In the context of diseases, loss-of-function experiments have shown diverse roles. In cardiac fibrosis, silencing CRLF1 in neonatal mice cardiac fibroblasts reversed the effects of increased cell viability, collagen production, and myofibroblast transformation induced by TGF-β1, indicating its role in aggravating cardiac fibrosis through the ERK1/2 signalling pathway [2]. In ovarian cancer, binding-defective CRLF1 variants impaired the interaction between AKT and SIN1, promoting pyroptosis and chemosensitization, suggesting that CRLF1 critically regulates chemoresistance in ovarian cancer [3]. In the ligamentum flavum hypertrophy, knockdown of CRLF1 reduced fibrosis caused by inflammatory cytokines and mechanical stress, and CRLF1 knockdown also impeded the formation of HLF in bipedal standing mice, revealing its crucial role in this process [4].

In summary, CRLF1 plays significant roles in multiple biological processes and disease conditions. Model-based research, especially loss-of-function experiments, has been crucial in revealing its functions in diseases such as cardiac fibrosis, ovarian cancer, and ligamentum flavum hypertrophy, providing potential therapeutic targets for these diseases.

References:

1. Crisponi, Laura, Buers, Insa, Rutsch, Frank. 2022. CRLF1 and CLCF1 in Development, Health and Disease. In International journal of molecular sciences, 23, . doi:10.3390/ijms23020992. https://pubmed.ncbi.nlm.nih.gov/35055176/

2. Luo, Shenjian, Yang, Zhi, Chen, Ruxin, Li, Jin, Zhang, Huijie. . Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway. In Journal of Zhejiang University. Science. B, 24, 682-697. doi:10.1631/jzus.B2200506. https://pubmed.ncbi.nlm.nih.gov/37551555/

3. Xiang, Cong, Chen, Li, Zhu, Shilei, Lei, Yunlong, Cai, Xiongwei. 2024. CRLF1 bridges AKT and mTORC2 through SIN1 to inhibit pyroptosis and enhance chemo-resistance in ovarian cancer. In Cell death & disease, 15, 662. doi:10.1038/s41419-024-07035-4. https://pubmed.ncbi.nlm.nih.gov/39256356/

4. Zheng, Zhenyu, Ao, Xiang, Li, Peng, Zhang, Zhongmin, Wang, Liang. 2020. CRLF1 Is a Key Regulator in the Ligamentum Flavum Hypertrophy. In Frontiers in cell and developmental biology, 8, 858. doi:10.3389/fcell.2020.00858. https://pubmed.ncbi.nlm.nih.gov/33072735/