Calcium-sensing receptor (CaSR) drives lung ECM remodelling and fibrosis in murine asthma models and in ageing mice

Macrophage plasticity—A matter of timing and mechanical load

“…In particular, the relevance of CaSR/TRPV4 in remodeling processes and foam cell development seen in fibrotic lungs and atherosclerotic plaques suggest a persistent pathophysiological phase of CaSR/TRPV4 signaling under mechanical stress in chronic inflammation. This notion is supported by recent studies showing that TRPV4 drives foam cell formation 6 and that CaSR activation mediates remodeling in pulmonary fibrosis 7 (Figure 1). Thus, it appears that macrophage plasticity is tightly regulated by various extracellular signals, such as [Ca 2+ ] e and LPS as well as the mechanical properties of the microenvironment, for example, extracellular matrix composition, which is adjusted and integrated by the CaSR/TRPV4 axis.…”