TRPV4 and fibrosis: The major findings of the current study are: (a) fibrosis-induced skin tissue stiffening is dependent on TRPV4 as determined by atomic force microscopy; (b) stiffness-dependent switch of macrophages to the M1 phenotype is reliant on TRPV4 in vivo; (c) soluble factors and increased substrate stiffness can act in a synergistic manner to upregulate the expression of macrophage M1 markers in vitro in a TRPV4-dependent manner; and (d) absolute TRPV4 dependence of matrix stiffness-induced expression of M1 markers was shown by gain-of-function of TRPV4 in TRPV4 KO macrophages.