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

Journal of Pathology - Tập 212 Số 2 - Trang 180-187 - 2007
M. J. Chung1, T Liu2, Matt Ullenbruch2, Sem H. Phan2
1Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109–2200, USA.
2Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA

Tóm tắt

AbstractMyofibroblasts 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)1 can induce myofibroblast differentiation and has an antiapoptotic effect on embryonic lung explant cultures. In this study, we investigated whether FIZZ1 also has an antiapoptotic effect on mouse lung fibroblasts (MLFs). Cells were treated with FIZZ1 for 24 h and then apoptosis was induced by TNFα in the presence of cycloheximide (CHX). FIZZ1 exhibited an antiapoptotic effect in MLFs, as assessed by flow cytometric analysis and TUNEL staining. Moreover, the cell number was higher in the FIZZ1‐treated group relative to the non‐treated control group after treatment with TNFα and CHX. FIZZ1 treatment also inhibited the apoptotic agent‐induced activities of caspase‐3 and caspase‐8. Examination of potential signalling pathways revealed that FIZZ1 induced rapid phosphorylation of ERK‐1/2, while PD98059, a MEK/ERK inhibitor, markedly induced activation of caspase‐3. This anti‐apoptotic 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 FIZZ1 was mediated by inhibition of caspase‐3 and ‐8, with involvement of the ERK pathway. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Từ khóa


Tài liệu tham khảo

10.1093/emboj/19.15.4046

10.1073/pnas.98.2.502

10.1016/S0888-7543(03)00070-3

10.1016/S0002-9440(10)63218-X

10.4049/jimmunol.173.5.3425

10.1161/01.RES.0000073999.07698.33

10.1152/ajplung.00168.2006

10.1016/S0165-2478(02)00225-0

10.1189/jlb.71.4.597

10.1165/rcmb.2003-0319OC

10.1172/JCI111953

Desmouliere A, 1995, Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar, Am J Pathol, 146, 56

10.1002/1529-0131(200010)43:10<2230::AID-ANR10>3.0.CO;2-8

Darby I, 1990, Alpha‐smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing, Lab Invest, 63, 21

10.1126/science.173.3996.548

Kuhn C, 1991, The roles of the myofibroblast in idiopathic pulmonary fibrosis. Ultrastructural and immunohistochemical features of sites of active extracellular matrix synthesis, Am J Pathol, 138, 1257

10.1002/path.1711050103

10.1046/j.1523-1747.1998.00095.x

10.1165/ajrcmb.21.6.3720

10.4049/jimmunol.158.3.1392

10.4049/jimmunol.172.1.560

10.1016/j.febslet.2006.03.027

10.1126/science.270.5240.1326

10.1091/mbc.11.3.1103

10.1038/sj.onc.1203805

10.1074/jbc.C000684200

10.1016/S0955-0674(98)80149-X

10.1046/j.1432-1327.2001.01936.x

10.1101/gad.13.22.2905

10.1165/rcmb.2005-0424OC

10.1074/jbc.M503065200

10.1038/ncb1005

10.1091/mbc.01-06-0291

Thông tin
Thông tin xuất bản

Journal of Pathology

Tập 212 Số 2

180-187

Thông tin tác giả