Cited by 551Cellular Mechanics and InteractionsTissue Engineering and Regenerative MedicineElasticity and Material Modeling

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Targeting extracellular matrix stiffness to attenuate disease: From molecular mechanisms to clinical trials

Lampi, Marsha C., Reinhart-King, Cynthia A.·2018·Science Translational Medicine

DOI 10.1126/scitranslmed.aao0475

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Abstract

Tissues stiffen during aging and during the pathological progression of cancer, fibrosis, and cardiovascular disease. Extracellular matrix stiffness is emerging as a prominent mechanical cue that precedes disease and drives its progression by altering cellular behaviors. Targeting extracellular matrix mechanics, by preventing or reversing tissue stiffening or interrupting the cellular response, is a therapeutic approach with clinical potential. Major drivers of changes to the mechanical properties of the extracellular matrix include phenotypically converted myofibroblasts, transforming growth factor β (TGFβ), and matrix cross-linking. Potential pharmacological interventions to overcome extracellular matrix stiffening are emerging clinically. Aside from targeting stiffening directly, alternative approaches to mitigate the effects of increased matrix stiffness aim to identify and inhibit the downstream cellular response to matrix stiffness. Therapeutic interventions that target tissue stiffening are discussed in the context of their limitations, preclinical drug development efforts, and clinical trials.

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Discher, D. E., Janmey, P., & Wang, Y.-L. (2005) · Science · doi:10.1126/science.1116995 · Cited by 6,382
Role of YAP/TAZ in mechanotransduction
Dupont, S., Morsut, L., Aragona, M., Enzo, E., Giulitti, S., Cordenonsi, M., Zanconato, F., Le Digabel, J., Forcato, M., Bicciato, S., et al. (2011) · Nature · doi:10.1038/nature10137 · Cited by 5,979
The Nuclear Factor NF- B Pathway in InflammationPreprint
Lawrence, T. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001651 · Cited by 5,126
Remodelling the extracellular matrix in development and disease
Bonnans, C., Chou, J., & Werb, Z. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3904 · Cited by 4,367
The biology and function of fibroblasts in cancer
Kalluri, R. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.73 · Cited by 4,366
The extracellular matrix at a glance
Frantz, C., Stewart, K. M., & Weaver, V. M. (2010) · Journal of Cell Science · doi:10.1242/jcs.023820 · Cited by 4,334
Tensional homeostasis and the malignant phenotype
Paszek, M. J., Zahir, N., Johnson, K. R., Lakins, J. N., Rozenberg, G. I., Gefen, A., Reinhart-King, C. A., Margulies, S. S., Dembo, M., Boettiger, D., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.08.010 · Cited by 3,941
Self-citation
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Özdemir, B. C., Pentcheva-Hoang, T., Carstens, J. L., Zheng, X., Wu, C.-C., Simpson, T. R., Laklai, H., Sugimoto, H., Kahlert, C., Novitskiy, S. V., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.005 · Cited by 2,681
Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion
Yeung, T., Georges, P. C., Flanagan, L. A., Marg, B., Ortiz, M., Funaki, M., Zahir, N., Ming, W., Weaver, V., & Janmey, P. A. (2005) · Cell Motility and the Cytoskeleton · doi:10.1002/cm.20041 · Cited by 2,325
Mechanotransduction and extracellular matrix homeostasis
Humphrey, J. D., Dufresne, E. R., & Schwartz, M. A. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3896 · Cited by 2,124

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Authors: Lampi, M. C., & Reinhart-King, C. A.
Affiliations: Cornell University (US)
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37212, USA.
ORCID: Lampi, Marsha C.
Reinhart-King, Cynthia A.
Venue: Science Translational Medicine
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2018-01-03
Volume: 10
Issue: 422
ISSN: 1946-6234 (ISSN-L)
1946-6242
DOI: 10.1126/scitranslmed.aao0475
OpenAlex: W2781877987
Cited by: 551
References: 159
Citations by year: 2026: 50 · 2025: 68 · 2024: 57 · 2023: 77 · 2022: 81 · 2021: 69 · 2020: 72 · 2019: 43 · 2018: 32
FWCI: 6.09
Type: journal article
Language: en
Open access: closed
Locations: Science Translational Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation (award333523, 1435755, award333525, 2013155462)
Ford Foundation (award333526)
National Heart, Lung, and Blood Institute (award333524, HL127499)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Physical Sciences › Engineering › Biomedical Engineering › Elasticity and Material Modeling
Keywords: extracellular matrix stiffness, tissue stiffening, mechanotransduction, myofibroblasts, TGF-beta, tumor progression, fibrosis, cardiovascular disease, aging, pharmacological interventions, drug development, clinical trials
MeSH terms: Animals, Cell Differentiation, Extracellular Matrix, Fibrosis, Humans, Transforming Growth Factor beta, Myofibroblasts

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Targeting extracellular matrix stiffness to attenuate disease: From molecular mechanisms to clinical trials

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