MARCH8 downregulation modulates profibrotic responses including myofibroblast differentiation

Abstract

MARCH8 is an important modulator of inflammation, immunity, and other cellular processes. We found that MARCH8 expression is downregulated in the lungs of patients with idiopathic pulmonary fibrosis (IPF) and experimental models of pulmonary fibrosis. Furthermore, TGF-β1 decreases MARCH8 transcriptionally in human lung fibroblasts (HLFs). MARCH8 overexpression blunts TGF-β1-induced fibroblast to myofibroblast transition while knockdown of MARCH8 drives this profibrotic change in HLFs. The findings support further exploration of MARCH8 as a novel target in IPF.