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

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

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

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.

Integrity signals

Registry

Crossref · 10.1126/scitranslmed.aao0475

Cites

157 of 157 references verified0 citation errors · 0 not checkable

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  • MRG-201 is a synthetic miRNA mimic of miR-29 designed to reduce the expression of collagen and other scar formation related proteins.

    “MRG-201 is a synthetic miRNA mimic of miR-29 designed to reduce the expression of collagen and other scar formation related proteins.[238, 241]”

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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.
Venue
Science Translational Medicine
Published
2018-01-03
Volume
10
Issue
422
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
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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