Antiapoptotic effect of found in inflammatory zone (FIZZ)1 on mouse lung fibroblasts

Myofibroblasts play an essential role in the abnormal deposition of extracellular matrix in pulmonary fibrosis. The presence or prolonged survival of these cells may be a key factor in the pathogenesis of progressive pulmonary fibrosis. Found in inflammatory zone (FIZZ)l can induce myofibroblast differentiation and has an antiapoptotic effect on embryonic lung explant cultures. In this study, we investigated whether FIZZI also has an antiapoptotic effect on mouse lung fibroblasts (NILFs). Cells were treated with FIZZ1 for 24 h and then apoptosis was induced by TNF alpha in the presence of cycloheximide (CHX). FIZZ1 exhibited an antiapoptotic effect in NILFs, as assessed by How cytometric analysis and TUNEL staining. Moreover, the cell number was higher in the FIZZ1-treated group relative to the nontreated control group after treatment with TNFa and CHX. FIZZ1 treatment also inhibited the apoptotic agent-induced activities of caspase-3 and caspase-8. Examination of potential signalling pathways revealed that FIZZI induced rapid phosphorylation of ERK-1/2, while PD98059, a MEK/ERK inhibitor, markedly induced activation of caspase-3. This antiapoptotic effect of FIZZ1 was associated with induction of myofibroblast differentiation in response to FIZZ1 stimulation. Taken together, these findings suggest that FIZZ1 is involved in pulmonary fibrosis through both induction of myofibroblast differentiation and increased or prolonged survival of myofibroblasts. This effect of FIZZI was mediated by inhibition of caspase-3 and -8, with involvement of the ERK pathway. Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.