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

The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index.

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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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.
ORCID
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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