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Fibroblast activation protein: a serine protease expressed at the remodeling interface in idiopathic pulmonary fibrosis
Abstract
Fibroblast activation protein (FAPalpha) is a member of the cell surface dipeptidyl peptidase (DPP) family of serine proteases. In its dimer form, FAPalpha exhibits gelatinase, collagenase, and DPP activity in vitro. Reactive fibroblasts in healing wounds and stromal fibroblasts associated with epithelial tumors express FAPalpha. Idiopathic pulmonary fibrosis (IPF) is a disease of the lung characterized by progressive fibrosis with no clear etiology or molecular marker for disease activity. Recently, it has been shown that fibroblast FAPalpha expression is induced in liver cirrhosis, with an expression pattern distinct from alpha-smooth muscle actin (alpha-SMA). In this study, we determine whether FAPalpha expression is selectively induced in areas of ongoing tissue remodeling characterized by fibroblast foci in IPF. Human lung tissue was obtained from patients with IPF, centrilobular emphysema, and normal lung. Immunohistochemical studies were performed using anti-FAPalpha antibody and antibodies against alpha-SMA and CD26 (DPPIV), another member of the DPP family. We found that FAPalpha was not expressed in normal human lung tissue or tissue with evidence of centriacinar emphysema, but was induced in all patients with IPF and With a pattern distinct from that of CD26 found primarily on hyperplastic alveolar epithelium. Specifically, FAPalpha was detected in fibroblast foci and in fibrotic interstitium and not in the interstitium of adjacent architecturally normal lung. Alveolar/airway epithelium and vascular smooth muscle did not express FAPalpha. This is the first report of FAPalpha expression in IPF and our results suggest that FAPalpha is selectively induced in fibrotic foci, but not in normal or emphysematous lung. Future studies will address whether FAPalpha may be used as a marker for disease activity in IPF.
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“FAP is expressed exclusively in fibrotic loci in the lungs of patients with IPF59”
From A generative AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis: a randomized phase 2a trial (2025) · cites this paper as [59]
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Cites
(2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.165.2.ats01 · Cited by 4,196
Desmoulière, A., Geinoz, A., Gabbiani, F., & Gabbiani, G. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.122.1.103 · Cited by 2,269
Transforming growth factor beta
Roberts, A. B., & Sporn, M. B. (2011) · SpringerReference · doi:10.1007/springerreference_39918 · Cited by 1,945
Selman, M., King, T. E., & Pardo, A. (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-134-2-200101160-00015 · Cited by 1,807
Idiopathic Pulmonary Fibrosis: Clinical Relevance of Pathologic Classification
KATZENSTEIN, A.-L. A., & MYERS, J. L. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.157.4.9707039 · Cited by 1,261
Self-citationIredale, J. P., Benyon, R. C., Pickering, J., McCullen, M., Northrop, M., Pawley, S., Hovell, C., & Arthur, M. J. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1018 · Cited by 1,075
Sappino, A. P., Schürch, W., & Gabbiani, G. (1990) · PubMed · Cited by 833
Transforming Growth Factor‐β: Major Role in Regulation of Extracellular Matrix
ROBERTS, A. B., HEINE, U. I., FLANDERS, K. C., & SPORN, M. B. (1990) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1990.tb17931.x · Cited by 696
Mechanisms of Myofibroblast Activity and Phenotypic Modulation
Serini, G., & Gabbiani, G. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4543 · Cited by 592
Park, J. E., Lenter, M., Zimmermann, R., Garin‐Chesa, P., Old, L. J., & Rettig, W. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.51.36505 · Cited by 591
Scanlan, M. J., Raj, B. K. M., Calvo, B. F., Garin‐Chesa, P., Sanz-Moncasi, M. P., Healey, J. H., Old, L. J., & Rettig, W. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.12.5657 · Cited by 577
Zhang, K., Rekhter, M. D., Gordon, D., & Phan, S. H. (1994) · PubMed Central · Cited by 477
Demedts, M., & Costabel, U. (2002) · European Respiratory Journal · doi:10.1183/09031936.02.00492002 · Cited by 460
Levy, M. T., McCaughan, G. W., Abbott, C. A., Park, J. E., Cunningham, A. M., Müller, E., Rettig, W. J., & Gorrell, M. D. (1999) · Hepatology · doi:10.1002/hep.510290631 · Cited by 338
Khalil, N., O'Connor, R. N., Flanders, K. C., & Unruh, H. W. (1996) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.14.2.8630262 · Cited by 328
Rettig, W. J., Garin‐Chesa, P., Beresford, H. R., Oettgen, H. F., Melamed, M. R., & Old, L. J. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.9.3110 · Cited by 271
Amino-terminal Truncation of Chemokines by CD26/Dipeptidyl-peptidase IV
Proost, P., Meester, I. D., Schols, D., Struyf, S., Lambeir, A., Wuyts, A., Opdenakker, G., Clercq, E. D., Scharpé, S., & Damme, J. V. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.13.7222 · Cited by 264
Chambers, R. C., Leoni, P., Kaminski, N., Laurent, G. J., & Heller, R. A. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63847-3 · Cited by 255
The thyroid hormone-induced tail resorption program during Xenopus laevis metamorphosis.
Brown, D. D., Wang, Z., Furlow, J. D., Kanamori, A., Schwartzman, R. A., Remo, B. F., & Pinder, A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.5.1924 · Cited by 245
Zhang, H.-Y., Gharaee‐Kermani, M., Zhang, K., Karmiol, S., & Phan, S. H. (1996) · Europe PMC (PubMed Central) · Cited by 235
Barbas‐Filho, J. V., Ferreira, M. A., Sesso, A., Kairalla, R. A., Carvalho, C. R. R., & Capelozzi, V. L. (2001) · Journal of Clinical Pathology · doi:10.1136/jcp.54.2.132 · Cited by 228
A Role for Dipeptidyl Peptidase IV in Suppressing the Malignant Phenotype of Melanocytic Cells
Wesley, U., Albino, A., Tiwari, S., & Houghton, A. (1999) · Journal of Experimental Medicine · doi:10.1084/jem.190.3.311 · Cited by 207
Adams, S., Miller, G. T., Jesson, M. I., Watanabe, T., Jones, B. N., & Wallner, B. P. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0447 · Cited by 202
Rettig, W. J., Garin‐Chesa, P., Healey, J. H., Su, S. L., Ozer, H. L., Schwab, M. G., Albino, A. P., & Old, L. J. (1993) · PubMed · Cited by 188
Regulation of Fibroblast Migration on Collagenous Matrix by a Cell Surface Peptidase Complex
Ghersi, G., Dong, H., Goldstein, L. A., Yeh, Y., Häkkinen, L., Larjava, H., & Chen, W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202770200 · Cited by 167
Epithelial cell-fibroblast interactions in lung injury and repair.
Adamson, I. Y. R., Hedgecock, C., & Bowden, D. H. (1990) · PubMed · Cited by 161
Levy, M. T., McCaughan, G. W., Marinos, G., & Gorrell, M. D. (2002) · Liver International · doi:10.1034/j.1600-0676.2002.01503.x · Cited by 151
Kapançi, Y., Desmoulière, A., Pache, J. C., Redard, M., & Gabbiani, G. (1995) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.152.6.8520791 · Cited by 146
Phenotypic and functional features of myofibroblasts in sheep fetal wounds
Estes, J. M., Berg, J. S. V., Adzick, N. S., MacGillivray, T. E., Desmoulière, A., & Gabbiani, G. (1994) · Differentiation · doi:10.1046/j.1432-0436.1994.5630173.x · Cited by 142
Uhal, B. D., Joshi, I., True, A. L., Mundle, S. D., Raza, A., Pardo, A., & Selman, M. (1995) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1995.269.6.l819 · Cited by 142
Fibroblast activation protein: Purification, epitope mapping and induction by growth factors
Rettig, W. J., Su, S. L., Fortunato, S. R., Scanlan, M. J., Raj, B. K. M., Garin‐Chesa, P., Healey, J. H., & Old, L. J. (1994) · International Journal of Cancer · doi:10.1002/ijc.2910580314 · Cited by 118
Niedermeyer, J., Scanlan, M. J., Garin‐Chesa, P., Daiber, C., Fiebig, H., Old, L. J., Rettig, W. J., & Schnapp, A. (1997) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19970502)71:3 · Cited by 91
Natural Substrates of Dipeptidyl Peptidase IV
Meester, I. D., Durinx, C., Bal, G., Proost, P., Struyf, S., Goossens, F. J., Augustyns, K., & Scharpé, S. (2002) · Advances in experimental medicine and biology · doi:10.1007/0-306-46826-3_7 · Cited by 84
Fukuda, Y., Basset, F., Ferrans, V. J., & Yamanaka, N. (1995) · Human Pathology · doi:10.1016/0046-8177(95)90114-0 · Cited by 77
Fibroblast heterogeneity in physiological conditions and fibrotic disease
Jelaska, A., Strehlow, D., & Korn, J. H. (1999) · Springer Seminars in Immunopathology · doi:10.1007/bf00870301 · Cited by 74
Pulmonary Fibroblast Heterogeneity
Phipps, R. P. (1992) · Cited by 51
Hepatic stellate cells reversibly express α-smooth muscle actin during acute hepatic ischemia
Rubbia‐Brandt, L., Mentha, G., Desmoulière, A., Costa, A. M. A., Giostra, E., Molas, G., Enzan, H., & Gabbiani, G. (1997) · Transplantation Proceedings · doi:10.1016/s0041-1345(97)00415-6 · Cited by 28
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Fingerlin, T. E., Murphy, E., Zhang, W., Peljto, A. L., Brown, K. K., Steele, M. P., Loyd, J. E., Cosgrove, G. P., Lynch, D., Groshong, S., et al. (2013) · Nature Genetics · doi:10.1038/ng.2609 · Cited by 809
Wang, L.-C. S., Lo, A., Scholler, J., Sun, J., Majumdar, R. S., Kapoor, V., Antzis, M., Cotner, C. E., Johnson, L. A., Durham, A. C., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0027 · Cited by 653
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Santos, A., Jung, J. J., Aziz, N., Kissil, J. L., & Puré, E. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38988 · Cited by 436
Self-citationIdiopathic Pulmonary Fibrosis: Aberrant Recapitulation of Developmental Programs?
Selman, M., Pardo, A., & Kaminski, N. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050062 · Cited by 342
Metadata
- Authors
- Acharya, P. S., Zukas, A., Chandan, V., Katzenstein, A.-L. A., & Puré, E.
- Affiliations
- The Wistar Institute (US)
- SUNY Upstate Medical University (US)
- Corresponding author
- Acharya, Pinak S.
- Venue
- Human Pathology
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 37
- Issue
- 3
- Pages
- 352-360
- ISSN
- 0046-8177 (ISSN-L)
- OpenAlex
- W2018096662
- Cited by
- 204
- References
- 38
- Citations by year
- 2026: 13 · 2025: 25 · 2024: 16 · 2023: 25 · 2022: 20 · 2021: 11 · 2020: 11 · 2019: 5 · 2018: 5 · 2017: 14 · 2016: 9 · 2015: 8 · 2014: 6 · 2013: 9 · 2012: 6
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Pathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P50HL067663, P50-HL67663)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Peptidase Inhibition and Analysis
- Health Sciences › Medicine › Rheumatology › Systemic Sclerosis and Related Diseases
- Keywords
- fibroblast activation protein, idiopathic pulmonary fibrosis, serine protease, dipeptidyl peptidase, tissue remodeling, fibroblast foci, alpha-smooth muscle actin, CD26, emphysema, pulmonary fibrosis, disease markers
- MeSH terms
- Fibroblast Activation Protein Alpha, Antigens, Surface, Emphysema, Female, Fibroblasts, Humans, Immunoenzyme Techniques, Lung, Male, Membrane Proteins, Middle Aged, Endopeptidases, Pulmonary Fibrosis, Serine Endopeptidases, Gelatinases, Dipeptidyl Peptidase 4
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