F2rl1-KO Mouse

F2rl1, also known as F2R like trypsin receptor 1 and encoding protease-activated receptor-2 (PAR2), is a G-protein coupled receptor. PAR2 is activated by serine proteases and is involved in various physiological and pathological processes. It participates in inflammatory responses, pain sensation, and cell proliferation-related pathways, and is of great biological importance [1,3,5-10]. Genetic models, such as gene knockout (KO) mouse models, can be used to study its functions.

In a study on diabetic kidney disease (DKD), knockdown of F2rl1 significantly reduced the inflammatory response in palmitate-stimulated HK-2 cells. F2rl1 might exacerbate lipotoxicity-induced DKD through the modulation of the Hippo signaling pathway, suggesting that modulating F2rl1 expression could be a strategy to mitigate RTECs inflammatory damage in DKD [1]. In another study, in aging and renal injury models, PAR2-deficient kidneys were protected from adenine-and cisplatin-induced renal fibrosis and injury by reducing senescence and inflammation, indicating the role of F2rl1 in renal senescence [2]. In glioma U251 cells, interference with F2rl1 inhibited cell proliferation, and melittin treatment, which decreased F2rl1 expression, also inhibited cell proliferation, metastasis, and invasion [3].

In conclusion, F2rl1 plays crucial roles in inflammatory responses, lipotoxicity-induced kidney injury, renal senescence, and glioma cell proliferation. The use of KO mouse models in these studies has revealed its functions in specific disease-related biological processes, providing potential therapeutic targets for diseases like DKD, renal fibrosis, and glioma.

References:

1. Wang, Hui, Wang, Wei, Jiang, Yao, Chen, Yong Q, Zhu, Shenglong. 2024. F2RL1 Inhibition Alleviates Lipotoxicity-Induced Kidney Injury Through the Hippo Pathway in Diabetic Kidney Disease. In Inflammation, , . doi:10.1007/s10753-024-02215-y. https://pubmed.ncbi.nlm.nih.gov/39738821/

2. Ha, Sugyeong, Kim, Hyun Woo, Kim, Kyung Mok, Chung, Hae Young, Chung, Ki Wung. 2024. PAR2-mediated cellular senescence promotes inflammation and fibrosis in aging and chronic kidney disease. In Aging cell, 23, e14184. doi:10.1111/acel.14184. https://pubmed.ncbi.nlm.nih.gov/38687090/

3. Xu, Peng, Zhou, Jie, Xing, Xiaohui, Li, Mengyou, Xiao, Yilei. 2024. Melitoxin Inhibits Proliferation, Metastasis, and Invasion of Glioma U251 Cells by Down-regulating F2RL1. In Applied biochemistry and biotechnology, 196, 6234-6252. doi:10.1007/s12010-023-04841-y. https://pubmed.ncbi.nlm.nih.gov/38252207/