The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Fibrosis: ultimate and proximate causes
Open accessAbstract
Fibrotic disorders account for an increasing burden of disease-associated morbidity and mortality worldwide. Although numerous risk factors have been recognized, the etiologies of many of these clinical syndromes have not been identified, and they are often termed idiopathic or cryptogenic. Here, we provide an evolutionary perspective on fibrosis aimed at elucidating its etiopathogenesis. By asking the ultimate question of "why" this process evolved in multicellular organisms, we hope to uncover proximate explanations for "how" it causes disease in humans. We posit that physiological fibrosis-like reactions evolved as an essential process in host defense against pathogens and in normal wound healing. Based on this premise, we reason that pathological fibrosis is related to one or more of the following: unidentified infectious or noninfectious antigens, autoimmunity, impaired regenerative responses, and the antagonistically pleiotropic action of genes involved in wound healing or development. The importance of genetic susceptibility, epigenetics, aging, and the modern-day environment are highlighted. Consideration of both ultimate and proximate causation goes beyond philosophical cogitations, as it will better inform pathobiological mechanisms of disease and aid in the prevention and treatment of fibrotic diseases.
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López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982
Gurtner, G. C., Werner, S., Barrandon, Y., & Longaker, M. T. (2008) · Nature · doi:10.1038/nature07039 · Cited by 6,542
Bataller, R., & Brenner, D. A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24282 · Cited by 4,958
Understanding the odd science of aging
Kirkwood, T. B. L. (2005) · Cell · doi:10.1016/j.cell.2005.01.027 · Cited by 1,984
Pleiotropy, natural selection, and the evolution of senescence
Williams, G. C. (1957) · Evolution · doi:10.2307/2406060 · Cited by 1,912
Fibrotic disease and the TH1/TH2 paradigm
Wynn, T. A. (2004) · Nature Reviews Immunology · doi:10.1038/nri1412 · Cited by 1,765
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
NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury
Hecker, L., Vittal, R., Jones, T., Jagirdar, R., Luckhardt, T. R., Horowitz, J. C., Pennathur, S., Martinez, F. J., & Thannickal, V. J. (2009) · Nature Medicine · doi:10.1038/nm.2005 · Cited by 852
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
Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance
Hecker, L., Logsdon, N. J., Kurundkar, D., Kurundkar, A., Bernard, K., Hock, T., Meldrum, E., Sanders, Y. Y., & Thannickal, V. J. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008182 · Cited by 686
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Wijsenbeek, M., & Cottin, V. (2020) · New England Journal of Medicine · doi:10.1056/nejmra2005230 · Cited by 736
Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets
Di, X., Gao, X., Peng, L., Ai, J., Jin, X., Qi, S., Li, H., Wang, K., & Luo, D. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01501-9 · Cited by 622
Glycolytic Reprogramming in Myofibroblast Differentiation and Lung Fibrosis
Xie, N., Tan, Z., Banerjee, S., Cui, H., Ge, J., Liu, R.-M., Bernard, K., Thannickal, V. J., & Liu, G. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201504-0780oc · Cited by 582
Self-citationMetformin reverses established lung fibrosis in a bleomycin model
Rangarajan, S., Bone, N. B., Zmijewska, A. A., Jiang, S., Park, D. W., Bernard, K., Locy, M. L., Ravi, S., Deshane, J., Mannon, R. B., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0087-6 · Cited by 560
Self-citationSingle-Cell Deconvolution of Fibroblast Heterogeneity in Mouse Pulmonary Fibrosis
Xie, T., Wang, Y., Deng, N., Huang, G., Taghavifar, F., Geng, Y., Liu, N., Kulur, V., Yao, C., Chen, P., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.010 · Cited by 527
Metadata
- Authors
- Thannickal, V. J., Zhou, Y., Gaggar, A., & Duncan, S. R.
- Venue
- Journal of Clinical Investigation
- Published
- 2014-11-03
- Volume
- 124
- Issue
- 11
- Pages
- 4673-4677
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2024447823
- Cited by
- 242
- References
- 17
- FWCI
- 15.27
- Type
- journal article
- Language
- en
- Open access
- bronze
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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