The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
WNT1-inducible signaling protein–1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis
Open accessAbstract
Idiopathic pulmonary fibrosis (IPF) is characterized by distorted lung architecture and loss of respiratory function. Enhanced (myo)fibroblast activation, ECM deposition, and alveolar epithelial type II (ATII) cell dysfunction contribute to IPF pathogenesis. However, the molecular pathways linking ATII cell dysfunction with the development of fibrosis are poorly understood. Here, we demonstrate, in a mouse model of pulmonary fibrosis, increased proliferation and altered expression of components of the WNT/beta-catenin signaling pathway in ATII cells. Further analysis revealed that expression of WNT1-inducible signaling protein-1 (WISP1), which is encoded by a WNT target gene, was increased in ATII cells in both a mouse model of pulmonary fibrosis and patients with IPF. Treatment of mouse primary ATII cells with recombinant WISP1 led to increased proliferation and epithelial-mesenchymal transition (EMT), while treatment of mouse and human lung fibroblasts with recombinant WISP1 enhanced deposition of ECM components. In the mouse model of pulmonary fibrosis, neutralizing mAbs specific for WISP1 reduced the expression of genes characteristic of fibrosis and reversed the expression of genes associated with EMT. More importantly, these changes in gene expression were associated with marked attenuation of lung fibrosis, including decreased collagen deposition and improved lung function and survival. Our study thus identifies WISP1 as a key regulator of ATII cell hyperplasia and plasticity as well as a potential therapeutic target for attenuation of pulmonary fibrosis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Moreover, transcript level as well as secretion of the ATII cell-derived fibrotic mediator Wnt-inducible signalling protein (Wisp) 1 [26] were significantly reduced upon senolytic treatment (online supplementary figure S5C and figure 5d; DMSO 2.10±0.91-fold over control versus DQ 0.71±0.26-fold over control).”
From Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo (2017) · cites this paper as [26]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Wnt Signaling Pathway in Development and Disease
Logan, C. Y., & Nusse, R. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.010403.113126 · Cited by 5,325
(2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.165.2.ats01 · Cited by 4,196
Epithelial-mesenchymal transition and its implications for fibrosis
Kalluri, R., & Neilson, E. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci20530 · Cited by 2,715
More powerful procedures for multiple significance testing
Hochberg, Y., & Benjamini, Y. (1990) · Statistics in Medicine · doi:10.1002/sim.4780090710 · Cited by 2,715
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
WNT and β-catenin signalling: diseases and therapies
Moon, R. T., Kohn, A. D., Ferrari, G. V. D., & Kaykas, A. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1427 · Cited by 1,763
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
Kim, K. K., Kugler, M. C., Wolters, P. J., Robillard, L., Galvez, M. G., Brumwell, A. N., Sheppard, D., & Chapman, H. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605669103 · Cited by 1,257
Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis
Phillips, R. J., Burdick, M. D., Hong, K. M., Lutz, M., Murray, L. A., Xue, Y., Belperio, J. A., Keane, M. P., & Strieter, R. M. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20997 · Cited by 1,071
TGF-β-induced EMT: mechanisms and implications for fibrotic lung disease
Willis, B. C., & Borok, Z. (2007) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00163.2007 · Cited by 1,064
Research works printed but not linked: 7
- Gharaee-Kermani, 2005, Methods Mol. Med., 117, 251
- Phan, 2003, Am. J. Respir. Cell Mol. Biol., 29, S87
- Kalluri, 2003, J. Clin. Invest., 112, 1776, 10.1172/JCI200320530 · DOI
- Uhal, 1998, Am. J. Physiol., 275, L1192
- Adamson, 1988, Am. J. Pathol., 130, 377
- Fukuda, 1985, Am. J. Pathol., 118, 452
- Phillips, 2004, J. Clin. Invest., 114, 438, 10.1172/JCI200420997 · DOI
Cited by
Sorted by citations
Mechanisms of fibrosis: therapeutic translation for fibrotic disease
Wynn, T. A., & Ramalingam, T. R. (2012) · Nature Medicine · doi:10.1038/nm.2807 · Cited by 3,541
King, T. E., Pardo, A., & Selman, M. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60052-4 · Cited by 2,194
Richeldi, L., Collard, H. R., & Jones, M. G. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30866-8 · Cited by 2,020
Integrating mechanisms of pulmonary fibrosis
Wynn, T. A. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20110551 · Cited by 1,326
Can we safely target the WNT pathway?
Kahn, M. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4233 · Cited by 1,063
Metadata
- Authors
- Königshoff, M., Kramer, M., Balsara, N., Wilhelm, J., Amarie, O. V., Jahn, A., Rose, F., Fink, L., Seeger, W., Schaefer, L., Günther, A., & Eickelberg, O.
- Affiliations
- Justus-Liebig-Universität Gießen (DE)
- Philipps University of Marburg (DE)
- Goethe University Frankfurt (DE)
- Helmholtz Munich (DE)
- Corresponding author
- Eickelberg, Oliver
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2009-03-16
- Volume
- 119
- Issue
- 4
- Pages
- 772-87
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2662540
- OpenAlex
- W2157101382
- Cited by
- 558
- References
- 72
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 29 · 2023: 22 · 2022: 25 · 2021: 27 · 2020: 36 · 2019: 26 · 2018: 44 · 2017: 41 · 2016: 53 · 2015: 42 · 2014: 33 · 2013: 42 · 2012: 40
- FWCI
- 30.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Site cant be reached (submittedVersion)
- Funders
- Alexander von Humboldt-Stiftung
- Deutsche Forschungsgemeinschaft
- Helmholtz Zentrum München
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- WISP1, idiopathic pulmonary fibrosis, alveolar type II cells, Wnt/β-catenin signaling, epithelial-mesenchymal transition, extracellular matrix deposition, myofibroblast activation, collagen deposition, pulmonary fibrosis, therapeutic target, neutralizing antibodies
- MeSH terms
- Adult, Animals, Bleomycin, Disease Models, Animal, Epithelial Cells, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Models, Biological, Proto-Oncogene Proteins, Pulmonary Alveoli, Pulmonary Fibrosis, Recombinant Proteins, Oncogene Proteins, Up-Regulation, Intracellular Signaling Peptides and Proteins, Cell Proliferation, Wnt Proteins, beta Catenin, Mice, Idiopathic Pulmonary Fibrosis, CCN Intercellular Signaling Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
