TRPV4, short for transient receptor potential cation channel subfamily V member 4, is a polymodal, non-selective, calcium-permeant cation channel. It is activated by endogenous and exogenous stimuli and participates in various physiological and pathological responses. TRPV4-expressing cells include both neuronal and non-neuronal types, and it responds to biochemical and biomechanical stimuli [1,2,4].

In macrophage-related studies, TRPV4-knockout in macrophages has shown significant results. In a mouse model, deletion of TRPV4 in macrophages suppresses allergic and non-allergic itch, suggesting its role in skin disease [1]. In a cecal slurry mouse model of sepsis, TRPV4 regulates sepsis-induced glycolysis, bacterial clearance in the peritoneum, and limits sepsis-induced lung injury, as it is required for glucose uptake through GLUT1 for effective phagolysosome maturation [3]. Also, TRPV4 knockout mice studies suggest that TRPV4 antagonism has therapeutic potential in oedema, pain, gastrointestinal disorders, and lung diseases such as cough, bronchoconstriction, pulmonary hypertension, and acute lung injury [2].

In conclusion, TRPV4 is crucial in multiple physiological and pathological processes. Model-based research, especially using TRPV4 KO mouse models, has revealed its significance in inflammatory conditions, sepsis-induced lung injury, and various other disease areas such as skin diseases, oedema, pain, and lung diseases. These findings provide insights into potential therapeutic strategies targeting TRPV4 [1,2,3].

References:

1. Dutta, Bidisha, Arya, Rakesh K, Goswami, Rishov, Sharma, Shweta, Rahaman, Shaik O. 2019. Role of macrophage TRPV4 in inflammation. In Laboratory investigation; a journal of technical methods and pathology, 100, 178-185. doi:10.1038/s41374-019-0334-6. https://pubmed.ncbi.nlm.nih.gov/31645630/

2. Grace, Megan S, Bonvini, Sara J, Belvisi, Maria G, McIntyre, Peter. 2017. Modulation of the TRPV4 ion channel as a therapeutic target for disease. In Pharmacology & therapeutics, 177, 9-22. doi:10.1016/j.pharmthera.2017.02.019. https://pubmed.ncbi.nlm.nih.gov/28202366/

3. Orsini, Erica M, Roychowdhury, Sanjoy, Gangadhariah, Mahesha, Vachharajani, Vidula, Scheraga, Rachel G. . TRPV4 Regulates the Macrophage Metabolic Response to Limit Sepsis-induced Lung Injury. In American journal of respiratory cell and molecular biology, 70, 457-467. doi:10.1165/rcmb.2023-0456OC. https://pubmed.ncbi.nlm.nih.gov/38346220/

4. Garcia-Elias, Anna, Mrkonjić, Sanela, Jung, Carole, Vicente, Rubén, Valverde, Miguel A. . The TRPV4 channel. In Handbook of experimental pharmacology, 222, 293-319. doi:10.1007/978-3-642-54215-2_12. https://pubmed.ncbi.nlm.nih.gov/24756711/