TIMP-1, -2, -3, and -4 in idiopathic pulmonary fibrosis. A prevailing nondegradative lung microenvironment?

American Journal of Physiology - Lung Cellular and Molecular Physiology - Tập 279 Số 3 - Trang L562-L574 - 2000
Moisés Selman1, Vı́ctor Ruiz1, Sandra Cabrera2, Lourdes Segura1, Remedios Ramı́rez2, Roberto Barrios3, Annie Pardo2
1Instituto Nacional de Enfermedades Respiratorias, México DF CP 14080, Mexico; and
2Facultad de Ciencias, Universidad Nacional Autonoma de Mexico, Coyocán México DF CP 04000;
3Department of Pathology, Baylor College of Medicine, Houston, Texas 77030.

Tóm tắt

Fibroblast proliferation and extracellular matrix accumulation characterize idiopathic pulmonary fibrosis (IPF). We evaluated the presence of tissue inhibitor of metalloproteinase (TIMP)-1, -2, -3, and -4; collagenase-1, -2, and -3; gelatinases A and B; and membrane type 1 matrix metalloproteinase (MMP) in 12 IPF and 6 control lungs. TIMP-1 was found in interstitial macrophages and TIMP-2 in fibroblast foci. TIMP-3 revealed an intense staining mainly decorating the elastic lamina in vessels. TIMP-4 was expressed in IPF lungs by epithelial and plasma cells. TIMP-2 colocalized with Ki67 in fibroblasts, whereas TIMP-3 colocalized with p27 in inflammatory and epithelial cells. Collagenase-1 was localized in macrophages and alveolar epithelial cells, collagenase-2 was localized in a few neutrophils, and collagenase-3 was not detected. MMP-9 was found in neutrophils and subepithelial myofibroblasts. Myofibroblast expression of MMP-9 was corroborated in vitro by RT-PCR. MMP-2 was noticed in myofibroblasts, some of them close to areas of basement membrane disruption, and membrane type 1 MMP was noticed in interstitial macrophages. These findings suggest that in IPF there is higher expression of TIMPs compared with collagenases, supporting the hypothesis that a nondegrading fibrillar collagen microenvironment is prevailing.

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Tài liệu tham khảo

10.1172/JCI1584

10.1177/10454411930040020401

10.1074/jbc.270.2.801

10.1159/000468613

10.1152/ajplung.1990.259.4.L159

Fukuda Y, 1998, Lab Invest, 78, 687

Gómez D, 1997, Eur J Cell Biol, 74, 111

10.1074/jbc.271.48.30375

10.1172/JCI2881

Hayakawa T, 1994, J Cell Sci, 107, 2373, 10.1242/jcs.107.9.2373

Hayashi T, 1996, Am J Pathol, 149, 1241

10.1074/jbc.272.24.15496

10.1172/JCI5461

10.1164/ajrccm.157.4.9707039

10.1164/ajrccm/140.6.1693

Kuhn C, 1991, Am J Pathol, 138, 1257

10.1165/ajrcmb.20.1.2941

10.1378/chest.96.5.1115

10.1016/S0002-9440(10)65625-8

10.1378/chest.102.4.1085

10.1164/ajrccm.154.4.8887609

10.1164/ajrccm/148.1.49

10.1164/ajrccm.160.4.9808006

10.1083/jcb.137.6.1445

Raghu G, 1985, Am Rev Respir Dis, 131, 281

10.1111/j.1699-0463.1999.tb01536.x

10.1378/chest.114.2.507

10.1016/0014-4800(89)90027-0

10.1136/thx.41.5.355

10.1378/chest.94.2.347

10.1006/cyto.1997.0233

The BAL Cooperative Group Steering Committee, 1990, Am Rev Respir Dis, 141, 188, 10.1164/ajrccm/141.5_Pt_2.S188

10.1152/ajplung.1998.275.6.L1192

10.1152/ajplung.1995.269.6.L819

10.1152/ajplung.1998.275.5.L998

10.1074/jbc.274.8.4570

10.1111/j.1749-6632.1994.tb24720.x

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American Journal of Physiology - Lung Cellular and Molecular Physiology

Tập 279 Số 3

L562-L574

Thông tin tác giả