Cadherin-11 integrates Piezo1 and interleukin-6 signaling to promote fibroblast activation.

ABSTRACT: Persistent fibroblast activation drives tissue fibrosis, yet how mechanical and inflammatory cues are integrated to promote this aberrant behavior remains unclear. Using a hyaluronic acid (HA)-based hydrogel platform to model normal and fibrotic lung mechanics, we examine the roles of Piezo1 and cadherin-11 (CDH11), both implicated in M2 macrophage-fibroblast crosstalk during pulmonary fibrosis progression, in interleukin (IL)-6-mediated fibroblast activation. While both Piezo1 and CDH11 expression increase in activated fibroblasts, blocking IL-6 signaling decreases CDH11, but not Piezo1, expression. Instead, Piezo1 activity promotes nuclear accumulation of the calcium-dependent transcription factor NFAT1. While Piezo1 inhibition moderately reduces CDH11 expression, it does not prevent fib

SUBMITTER: Astrab LR 

PROVIDER: S-EPMC12458258 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature