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Canonical Wnt signaling induces skin fibrosis and subcutaneous lipoatrophy: A novel mouse model for scleroderma?
Open accessAbstract
OBJECTIVE: Because aberrant Wnt signaling has been linked with systemic sclerosis (SSc) and pulmonary fibrosis, we sought to investigate the effect of Wnt-10b on skin homeostasis and differentiation in transgenic mice and in explanted mesenchymal cells. METHODS: The expression of Wnt-10b in patients with SSc and in a mouse model of fibrosis was investigated. The skin phenotype and biochemical characteristics of Wnt-10b-transgenic mice were evaluated. The in vitro effects of ectopic Wnt-10b were examined in explanted skin fibroblasts and preadipocytes. RESULTS: The expression of Wnt-10b was increased in lesional skin biopsy specimens from patients with SSc and in those obtained from mice with bleomycin-induced fibrosis. Transgenic mice expressing Wnt-10b showed progressive loss of subcutaneous adipose tissue accompanied by dermal fibrosis, increased collagen deposition, fibroblast activation, and myofibroblast accumulation. Wnt activity correlated with collagen gene expression in these biopsy specimens. Explanted skin fibroblasts from transgenic mice demonstrated persistent Wnt/β-catenin signaling and elevated collagen and α-smooth muscle actin gene expression. Wnt-10b infection of normal fibroblasts and preadipocytes resulted in blockade of adipogenesis and transforming growth factor β (TGFβ)-independent up-regulation of fibrotic gene expression. CONCLUSION: SSc is associated with increased Wnt-10b expression in the skin. Ectopic Wnt-10b causes loss of subcutaneous adipose tissue and TGFβ-independent dermal fibrosis in transgenic mice. These findings suggest that Wnt-10b switches differentiation of mesenchymal cells toward myofibroblasts by inducing a fibrogenic transcriptional program while suppressing adipogenesis. Wnt-10b-transgenic mice represent a novel animal model for investigating Wnt signaling in the setting of fibrosis.
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“In vitro, FIZZ1 suppresses adipogenesis and stimulates myofibroblast differentiation via Notch1 signaling.”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [89]
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“Adipocyte to myofibroblast transition is strongly driven by TGFβ (88), Found in inflammatory zone 1 (FIZZ1) and possibly Wnt signaling (89).”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [89]
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Cites
Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases
MacDonald, B. T., Tamai, K., & He, X. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.06.016 · Cited by 5,583
Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis
Brack, A. S., Conboy, M. J., Roy, S., Lee, M., Kuo, C. J., Keller, C., & Rando, T. A. (2007) · Science · doi:10.1126/science.1144090 · Cited by 1,564
Towards an integrated view of Wnt signaling in development
van Amerongen, R., & Nusse, R. (2009) · Development · doi:10.1242/dev.033910 · Cited by 1,213
Systemic sclerosis: a prototypic multisystem fibrotic disorder
Varga, J., & Abraham, D. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31139 · Cited by 1,187
Self-citationRam�rez-Zacar�as, J. L., Castro‐Muñozledo, F., & Kuri‐Harcuch, W. (1992) · Histochemistry and Cell Biology · doi:10.1007/bf00316069 · Cited by 1,009
Regulation of osteoblastogenesis and bone mass by Wnt10b
Bennett, C. N., Longo, K. A., Hahn, W. S., Suva, L. J., Lane, T. F., Hankenson, K. D., & MacDougald, O. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408742102 · Cited by 898
Self-citationAberrant Wnt/β-Catenin Pathway Activation in Idiopathic Pulmonary Fibrosis
Chilosi, M., Poletti, V., Zamò, A., Lestani, M., Montagna, L., Piccoli, P., Pedron, S., Bertaso, M., Scarpa, A., Murer, B., et al. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64282-4 · Cited by 708
Wnt signaling: is the party in the nucleus?Preprint
Willert, K., & Jones, K. A. (2006) · Genes & Development · doi:10.1101/gad.1424006 · Cited by 599
Königshoff, M., Kramer, M., Balsara, N., Wilhelm, J., Amarie, O. V., Jahn, A., Rose, F., Fink, L., Seeger, W., Schaefer, L., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci33950 · Cited by 558
Functional Wnt Signaling Is Increased in Idiopathic Pulmonary Fibrosis
Königshoff, M., Balsara, N., Pfaff, E.-M., Kramer, M., Chrobak, I., Seeger, W., & Eickelberg, O. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002142 · Cited by 511
Wnt signaling: complexity at the surface
Cadigan, K. M., & Liu, Y. I. (2006) · Journal of Cell Science · doi:10.1242/jcs.02826 · Cited by 486
Inhibition of Wnt/β-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis
Henderson, W. R., Chi, E. Y., Ye, X., Nguyen, C., Tien, Y.-T., Zhou, B., Borok, Z., Knight, D. A., & Kahn, M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001520107 · Cited by 466
Gene Expression Profiles Distinguish Idiopathic Pulmonary Fibrosis from Hypersensitivity Pneumonitis
Selman, M., Pardo, A., Barrera, L., Estrada, A., Watson, S. R., Wilson, K., Aziz, N. A., Kaminski, N., & Zlotnik, A. (2005) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200504-644oc · Cited by 455
Chen, S.-J., Yuan, W., Mori, Y., Levenson, A. S., Varga, J., & Trojanowska, M. E. (1999) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1999.00477.x · Cited by 411
Self-citationSystemic and cell type-specific gene expression patterns in scleroderma skin
Whitfield, M. L., Finlay, D. R., Murray, J. I., Troyanskaya, O. G., Chi, J., Pergamenschikov, A., McCalmont, T. H., Brown, P. O., Botstein, D., & Connolly, M. K. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1635114100 · Cited by 408
A Wnt Survival Guide: From Flies to Human Disease
Chien, A. J., Conrad, W. H., & Moon, R. T. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.445 · Cited by 382
Wnt10b Inhibits Development of White and Brown Adipose Tissues
Longo, K. A., Hahn, W. S., Kang, S., Gerin, I., Chiang, S.-H., Lucas, P. C., Opp, M. R., & MacDougald, O. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402937200 · Cited by 372
Self-citationWnt/β-catenin signaling in adipogenesis and metabolism
Prestwich, T. C., & MacDougald, O. A. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.09.014 · Cited by 364
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
Cheon, S. S., Cheah, A. Y. L., Turley, S., Nadesan, P., Poon, R. W. M., Clevers, H. C., & Alman, B. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.102657399 · Cited by 315
Transforming growth factor β as a therapeutic target in systemic sclerosis
Varga, J., & Pasche, B. (2009) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2009.26 · Cited by 298
Self-citationLee, C. H., Shah, B. S., Moioli, E. K., & Mao, J. J. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43230 · Cited by 298
Lee, C. H., Shah, B. S., Moioli, E. K., & Mao, J. J. (2015) · Journal of Clinical Investigation · doi:10.1172/jci84508 · Cited by 282
Wu, M., Melichian, D. S., Chang, E., Warner-Blankenship, M., Ghosh, A. K., & Varga, J. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.080574 · Cited by 236
Self-citationNarrative Review: Fibrotic Diseases: Cellular and Molecular Mechanisms and Novel Therapies
Rosenbloom, J., Castro, S. V., & Jimenez, S. A. (2010) · Annals of Internal Medicine · doi:10.7326/0003-4819-152-3-201002020-00007 · Cited by 230
Targeted Disruption of TGF-β/Smad3 Signaling Modulates Skin Fibrosis in a Mouse Model of Scleroderma
Lakos, G., Takagawa, S., Chen, S.-J., Ferreira, A. M., Han, G., Masuda, K., Wang, X., DiPietro, L. A., & Varga, J. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63289-0 · Cited by 216
Self-citationGhosh, A. K., Bhattacharyya, S., Lakos, G., Chen, S., Mori, Y., & Varga, J. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20104 · Cited by 201
Self-citationWei, J., Ghosh, A. K., Sargent, J. L., Komura, K., Wu, M., Huang, Q.-Q., Jain, M., Whitfield, M. L., Feghali‐Bostwick, C. A., & Varga, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013778 · Cited by 200
Self-citationSonnylal, S., Shiwen, X., Leoni, P., Naff, K. A., Pelt, C. S. V., Nakamura, H., Leask, A., Abraham, D., Bou–Gharios, G., & Crombrugghe, B. D. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27382 · Cited by 196
Mechanisms and consequences of fibrosis in systemic sclerosis
Denton, C. P., Black, C. M., & Abraham, D. (2006) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0115 · Cited by 181
Cellular origins of fibroblasts: possible implications for organ fibrosis in systemic sclerosis
Postlethwaite, A. E., Shigemitsu, H., & Kanangat, S. (2004) · Current Opinion in Rheumatology · doi:10.1097/01.bor.0000139310.77347.9c · Cited by 173
Lam, A. P., Flozak, A. S., Russell, S., Wei, J., Jain, M., Mutlu, G. M., Budinger, G. R. S., Feghali‐Bostwick, C. A., Varga, J., & Gottardi, C. J. (2011) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2010-0113oc · Cited by 156
Self-citationKrieg, T., Abraham, D., & Lafyatis, R. (2007) · Arthritis Research & Therapy · doi:10.1186/ar2188 · Cited by 151
Self-citationBayle, J., Fitch, J. L., Jacobsen, K. A., Kumar, R., Lafyatis, R., & Lemaire, R. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5701101 · Cited by 135
Self-citationTakagawa, S., Lakos, G., Mori, Y., Varga, J., Yamamoto, T., & Nishioka, K. (2003) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2003.12308.x · Cited by 122
Self-citationChang, W., Wei, K., Jacobs, S. S., Upadhyay, D., Weill, D., & Rosen, G. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.025684 · Cited by 116
He, W., Tan, R., Dai, C., Li, Y., Wang, D., Hao, S., Kahn, M., & Liu, Y. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.091256 · Cited by 110
Gustafson, B., & Smith, U. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.102855 · Cited by 104
Dermal Transforming Growth Factor-β Responsiveness Mediates Wound Contraction and Epithelial Closure
Martínez‐Ferrer, M., Sharif‐Afshar, A., Uwamariya, C., Crombrugghe, B. D., Davidson, J. M., & Bhowmick, N. A. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090283 · Cited by 96
Techniques for Studying Adipocytes
Hausman, G. (1981) · Stain Technology · doi:10.3109/10520298109067302 · Cited by 88
O’Brown, Z. K., Walmsley, G. G., Nusse, Y. M., Nusse, R., & Brown, P. O. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000945 · Cited by 84
Role for ICAT in β-catenin-dependent nuclear signaling and cadherin functions
Gottardi, C. J., & Gumbiner, B. M. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00433.2003 · Cited by 78
Self-citationWei, J., Bhattacharyya, S., & Varga, J. (2010) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e32833de1a7 · Cited by 77
Self-citationβ-Catenin has sequential roles in the survival and specification of ventral dermis
Ohtola, J. A., Myers, J., Akhtar‐Zaidi, B., Zuzindlak, D., Sandesara, P. B., Yeh, K., Mackem, S., & Atit, R. P. (2008) · Development · doi:10.1242/dev.021170 · Cited by 75
Immunolocalization of BMP-2/-4, FGF-4, and WNT10b in the Developing Mouse First Lower Molar
Nadiri, A., Kuchler‐Bopp, S., Haïkel, Y., & Lesot, H. (2004) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540405200110 · Cited by 70
The gene expression profile induced by Wnt 3a in NIH 3T3 fibroblasts
Chen, S., McLean, S., Carter, D. E., & Leask, A. (2007) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-007-0015-x · Cited by 60
WNTS and WNT receptors as therapeutic tools and targets in human disease processes
Andy, J. C. (2006) · Frontiers in bioscience · doi:10.2741/2074 · Cited by 55
Lemaire, R., Farina, G. A., Bayle, J., Dimarzio, M., Pendergrass, S. A., Milano, A., Whitfield, M. L., & Lafyatis, R. (2010) · Journal of Investigative Dermatology · doi:10.1038/jid.2010.15 · Cited by 53
Self-citationIn perspective: Murine models of scleroderma
Wu, M., & Varga, J. (2008) · Current Rheumatology Reports · doi:10.1007/s11926-008-0030-9 · Cited by 31
Self-citationBhattacharyya, S., Wei, J., Melichian, D. S., Milbrandt, J., Takehara, K., & Varga, J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007620 · Cited by 30
Self-citationPharmacotherapy of systemic sclerosis
Postlethwaite, A. E., Harris, L. J., Raza, S. H., Kodura, S., & Akhigbe, T. (2010) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656561003592177 · Cited by 23
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Akhmetshina, A., Palumbo, K., Dees, C., Bergmann, C., Venalis, P., Zerr, P., Horn, A., Kireva, T., Beyer, C., Zwerina, J., et al. (2012) · Nature Communications · doi:10.1038/ncomms1734 · Cited by 843
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Metadata
- Authors
- Wei, J., Melichian, D., Komura, K., Hinchcliff, M., Lam, A. P., Lafyatis, R., Gottardi, C. J., MacDougald, O. A., & Varga, J.
- Affiliations
- Northwestern University (US)
- Boston University (US)
- University of Michigan (US)
- ORCID
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2011-05-31
- Volume
- 63
- Issue
- 6
- Pages
- 1707-1717
- ISSN
- 0004-3591 (ISSN-L)
- PMC
- PMC3124699
- OpenAlex
- W1967131493
- Cited by
- 214
- References
- 52
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 12 · 2023: 6 · 2022: 8 · 2021: 18 · 2020: 12 · 2019: 14 · 2018: 13 · 2017: 22 · 2016: 23 · 2015: 18 · 2014: 13 · 2013: 16 · 2012: 23
- FWCI
- 13.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P30HL101292, R01HL094643, K08HL093216)
- National Institute of Diabetes and Digestive and Kidney Diseases (R56DK062876, DK-51563, N02 DK062876, R01DK051563, R01DK062876)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR49025, R01AR051089, R01AR049025)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Sclerosis and Related Diseases
- Health Sciences › Medicine › Rheumatology › Dupuytren's Contracture and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Keywords
- Wnt signaling, systemic sclerosis, skin fibrosis, myofibroblast differentiation, adipogenesis, collagen deposition, Wnt/β-catenin signaling, bleomycin-induced fibrosis, transgenic mouse model, dermal fibroblasts, preadipocytes
- MeSH terms
- Actins, Animals, Bleomycin, Collagen, Disease Models, Animal, Female, Fibroblasts, Fibrosis, Humans, Lipodystrophy, Mice, Transgenic, Scleroderma, Systemic, Skin, Gene Expression, Cell Culture Techniques, Adipogenesis, Wnt Proteins, beta Catenin, Mice, Myofibroblasts
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