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 IPF.
“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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- 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
- Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
- Health Sciences › Medicine › Pathology and Forensic Medicine › 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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