Figure 1.

Mechano-sensing by LSECs drives fibrotic processes. LSECs can respond to changes in shear stress and pressure in the sinusoid through activation of PIEZO channels. Data by Hilscher et al. (4) suggests this is triggered by integrins and myosin filaments. PIEZO channel activation drives cleavage of Notch to release NICD, and transcription of Notch pathway genes HES1 and HEY1. Activation of this mechanism results in chemokine secretion (CXCL1) which recruits neutrophils (a). Signaling by LSECs is also known to trigger HSC activation (b) which leads to stiffening of the ECM, potentially driving activation of other mechano-sensitive pathways (c) such as YAP1.