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Modelling and targeting mechanical forces in organ fibrosis
Open accessAbstract
Few efficacious therapies exist for the treatment of fibrotic diseases, such as skin scarring, liver cirrhosis and pulmonary fibrosis, which is related to our limited understanding of the fundamental causes and mechanisms of fibrosis. Mechanical forces from cell-matrix interactions, cell-cell contact, fluid flow and other physical stimuli may play a central role in the initiation and propagation of fibrosis. In this Review, we highlight the mechanotransduction mechanisms by which various sources of physical force drive fibrotic disease processes, with an emphasis on central pathways that may be therapeutically targeted to prevent and reverse fibrosis. We then discuss engineered models of mechanotransduction in fibrosis, as well as molecular and biomaterials-based therapeutic approaches for limiting fibrosis and promoting regenerative healing phenotypes in various organs. Finally, we discuss challenges within fibrosis research that remain to be addressed and that may greatly benefit from next-generation bioengineered model systems.
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“A seminal study demonstrated that Cadherin-11 facilitates robust adhesion between M2-like macrophages and myofibroblasts, creating a niche enriched with active TGF-b (3, 57, 63, 64).”
From The mechanotransduction-immune axis in organ fibrosis: dual regulatory mechanisms and translational therapeutic perspectives (2025) · cites this paper as [3]
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Metadata
- Authors
- Mascharak, S., L. Guo, J., Griffin, M., E. Berry, C., C. Wan, D., & T. Longaker, M.
- Affiliations
- Stanford Medicine (US)
- Venue
- Nature Reviews Bioengineering
- Published
- 2024-01-18
- Volume
- 2
- Issue
- 4
- Pages
- 305-323
- ISSN
- 2731-6092 (ISSN-L)
- PMC
- PMC11567675
- OpenAlex
- W4390964997
- Cited by
- 59
- References
- 226
- Citations by year
- 2026: 33 · 2025: 21 · 2024: 5
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Reviews Bioengineering (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (F32HL167318)
- National Institute of General Medical Sciences (R01GM136659)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR081343)
- National Institute of Dental and Craniofacial Research (R01DE027346, U24DE029463, R01DE032677)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- organ fibrosis, mechanotransduction, mechanical forces, cell-matrix interactions, cell-cell contact, fluid flow, pulmonary fibrosis, liver cirrhosis, scar tissue
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