Cited by 206Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisPeptidase Inhibition and AnalysisSystemic Sclerosis and Related Diseases

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Fibroblast activation protein: a serine protease expressed at the remodeling interface in idiopathic pulmonary fibrosis

Acharya, Pinak S., Zukas, Alicia, Chandan, Vishal, Katzenstein, Anna-Luise A., Puré, Ellen·2006·Human Pathology

DOI 10.1016/j.humpath.2005.11.020

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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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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.
ORCID: Zukas, Alicia
Chandan, Vishal
Puré, Ellen
Venue: Human Pathology
Publisher: Elsevier BV
Published: 2006-03
Volume: 37
Issue: 3
Pages: 352-360
ISSN: 0046-8177 (ISSN-L)
DOI: 10.1016/j.humpath.2005.11.020
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Fibroblast activation protein: a serine protease expressed at the remodeling interface in idiopathic pulmonary fibrosis

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