The DOI matches its Crossref record; 90 of the 91 references it cites were found in a registry or an index.
Peptidylarginine deiminase 4 promotes age-related organ fibrosis
Open accessAbstract
Aging promotes inflammation, a process contributing to fibrosis and decline in organ function. The release of neutrophil extracellular traps (NETs [NETosis]), orchestrated by peptidylarginine deiminase 4 (PAD4), damages organs in acute inflammatory models. We determined that NETosis is more prevalent in aged mice and investigated the role of PAD4/NETs in age-related organ fibrosis. Reduction in fibrosis was seen in the hearts and lungs of aged PAD4−/− mice compared with wild-type (WT) mice. An increase in left ventricular interstitial collagen deposition and a decline in systolic and diastolic function were present only in WT mice, and not in PAD4−/− mice. In an experimental model of cardiac fibrosis, cardiac pressure overload induced NETosis and significant platelet recruitment in WT but not PAD4−/− myocardium. DNase 1 was given to assess the effects of extracellular chromatin. PAD4 deficiency or DNase 1 similarly protected hearts from fibrosis. We propose a role for NETs in cardiac fibrosis and conclude that PAD4 regulates age-related organ fibrosis and dysfunction.
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“A previous study found that aged mice exhibited an increased propensity for NETosis compared to younger mice.”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [270]
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“This heightened NETosis activity was associated with the activation of peptidylarginine deiminase 4 (PAD4), an enzyme involved in the formation of NETs.”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [270]
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“The excessive formation of NETs, in turn, was implicated in the development of age-related organ fibrosis.270”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [270]
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Neutrophil Extracellular Traps Kill Bacteria
Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D. S., Weinrauch, Y., & Zychlinsky, A. (2004) · Science · doi:10.1126/science.1092385 · Cited by 10,268
Mizgerd, J. P., Kubo, H., Kutkoski, G. J., Bhagwan, S. D., Scharffetter-Kochanek, K., Beaudet, A. L., & Doerschuk, C. M. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.8.1357 · Cited by 7,332
Neutrophil recruitment and function in health and inflammation
Kolaczkowska, E., & Kubes, P. (2013) · Nature Reviews Immunology · doi:10.1038/nri3399 · Cited by 5,472
Theory and Practice of Histological Techniques
Goss, G. R. (2009) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e3181805089 · Cited by 5,454
Woessner, J. F. (1961) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(61)90291-0 · Cited by 3,849
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
Oxidative Stress, Caloric Restriction, and Aging
Sohal, R. S., & Weindruch, R. H. (1996) · Science · doi:10.1126/science.273.5271.59 · Cited by 3,133
Extracellular DNA traps promote thrombosis
Fuchs, T. A., Brill, A. G., Duerschmied, D., Schatzberg, D., Monestier, M., Myers, D. D., Wrobleski, S. K., Wakefield, T. W., Hartwig, J. H., & Wagner, D. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005743107 · Cited by 2,591
Self-citationJunqueira, L. C. U., Bignolas, G., & Brentani, H. (1979) · The Histochemical Journal · doi:10.1007/bf01002772 · Cited by 2,570
Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood
Clark, S. R., Ma, A. C., Tavener, S. A., McDonald, B., Goodarzi, Z., Kelly, M. M., Patel, K. D., Chakrabarti, S., McAvoy, E., Sinclair, G. D., et al. (2007) · Nature Medicine · doi:10.1038/nm1565 · Cited by 2,309
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1 of the 91 references couldn’t be matched to a known paper.
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- Bancroft, 2008, Connective tissue and stains, 135
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Haverich, A., & Boyle, E. C. (2023) · Springer eBooks · doi:10.1007/978-3-031-31766-8_5
Sharma, D., & Kumar, R. K. (2024) · Exploration of neuroscience · doi:10.37349/en.2024.00056
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Rashidova, S. S., Алановна, М. Д., Tuganova, A. Z., Albastova, D. T., Bagaeva, V. T., Dzaparova, A. A., Taugazova, L. A., Ataeva, Y. V., Krupnova, E. I., Shakhramanov, A. E., et al. (2024) · HERALD of North-Western State Medical University named after I I Mechnikov · doi:10.17816/mechnikov636568
Meng, H. C., Han, Y., Yang, J., & Wang, P. (2025) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2025.06.032
Lei, J., Zhao, M., Yao, S., Lu, M., Deng, F., Xu, T., Zhang, M., Sun, M., & Gao, Q. (2025) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.125.323061
Nording, H., Baron, L., Sauter, M., Hagemann, L., von Esebeck, J., Schommer, N., Duerschmied, D., Marquardt, J. U., Lerchenmüller, C., Zürn, C., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.12.699090
Mei, X., Saha, P., Mell, B., Zeydabadinejad, S., Yeoh, B. S., Gohara, A. F., Vijay–Kumar, M., & Joe, B. (2026) · iScience · doi:10.1016/j.isci.2026.115651
Zhang, W., Yi, J., & Li, Z. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1847027
Sha, L., & Jha, S. (2026) · Advances in immunology · doi:10.1016/bs.ai.2026.04.008
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Swenson, G. E., & Fischer, M. A. (2026) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00127.2026
Hofbauer, T. M., Ondracek, A. S., Artner, T., Aszlan, A., Hofer, F., Kazem, N., Hammer, A., Brekalo, M., Zimpfer, D., Steinlechner, B., et al. (2026) · Heart Rhythm · doi:10.1016/j.hrthm.2026.07.027
Al-U'datt, D. G. F., Tashtush, A. A., Al-U’datt, M., Tranchant, C. C., Al-masaed, S., & Jaradat, S. A. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.179239
Xie, J., Meng, D., Weng, J., & Lai, Z. (2026) · Vascular Pharmacology · doi:10.1016/j.vph.2026.107705
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Metadata
- Authors
- Martinod, K., Witsch, T., Erpenbeck, L., Savchenko, A., Hayashi, H., Cherpokova, D., Gallant, M., Mauler, M., Cifuni, S. M., & Wagner, D. D.
- Affiliations
- Boston Children's Hospital (US)
- University of Freiburg (DE)
- Corresponding author
- Wagner, Denisa D.
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2016-12-28
- Volume
- 214
- Issue
- 2
- Pages
- 439-458
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC5294849
- OpenAlex
- W2562661149
- Cited by
- 218
- References
- 91
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 36 · 2023: 28 · 2022: 20 · 2021: 25 · 2020: 22 · 2019: 21 · 2018: 19 · 2017: 10
- FWCI
- 10.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- GRO (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL102101, R01HL125501, 5T32HL066987-13)
- Boston Children’s Hospital
- Deutsche Forschungsgemeinschaft (CH 1734/1-1)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Keywords
- PAD4, neutrophil extracellular traps, NETosis, myocardial fibrosis, pulmonary fibrosis, aging, inflammation, DNase1, platelet recruitment, pressure overload, collagen deposition, cardiac function
- MeSH terms
- Protein-Arginine Deiminase Type 4, Age Factors, Animals, Collagen, Fibrosis, Hydrolases, Mice, Inbred C57BL, Myocardium, Pulmonary Fibrosis, Ventricular Function, Left, Reactive Oxygen Species, Mice, Extracellular Traps
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