Chronic inflammation can damage previously healthy tissues and organs, leading to a number of ailments including cardiovascular disease, rheumatoid arthritis, and lupus. Activation and deactivation of calcium-importing ion channel TRPV4 modulates inflammation through multiple mechanisms. Indeed, it has been shown that TRPV4 antagonists reduce production of pro-inflammatory cytokines, while TRPV4 activation shifts macrophages to more pro-inflammatory phenotypes. Using human cell models, Babaniamansour et al. highlight the role of regulating the TRPV4 activity of macrophages to influence the phenotypic commitment and extracellular matrix-macrophage interaction.

Collagen is a major component of the extracellular matrix in all cell types. Collagen can be detected by Masson’s trichrome, while damaged collagen can be visualized and quantified by Biotin-conjugated Collagen Hybridizing Peptides (B-CHPs). Streptavidin-conjugated fluorescent dye markers allow for visualization of the damaged collagen, to which CHPs selectively bind. Using Masson’s trichrome, they found a less dense collagen network in the cells treated with a TRPV4 agonist (shown in the Figure). Using B-CHPs, they additionally found that the degradation of the collagen network was higher in cells treated with the TRPV4 agonist, which simulates calcium entry. Overall, the authors successfully use B-CHPs to examine structural changes of the macrophage collagen matrix after TRPV4 activation with a pharmacological agent.