Figure 7.

Model of mechanism of the antifibrotic function of FRNK. Injury or profibrotic stimuli, such as TGF-β1, activate fibroblasts, induce integrin-mediated and growth factor–initiated signaling, such as through FAK, Rac, Rho, and S100A4, promote cell migration and recruitment of cells to sites of injury, and promote cell contraction and fibrotic responses. These profibrotic signals also promote myofibroblast differentiation and ECM production, partly through FAK and mitogen-activated protein kinases (MAPKs; eg, ERK and p38). FRNK functions to limit these responses, including cell migration, myofibroblast differentiation, and ECM production. Under conditions of impaired FRNK function, as in down-regulated FRNK in IPF, these profibrotic responses are amplified, resulting in the development of an exuberant fibrotic process and expansion of fibrotic lesions.