ArticleThe Journal of biological chemistry2012
Corneal antifibrotic switch identified in genetic and pharmacological deficiency of vimentin.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Fibroblast response to burn injury in larval zebrafish mirrors developmental maturation and is inhibited by infiltrating neutrophils.Development (Cambridge, England) · 2026Article
- Intermediate filaments and their associated molecules.Journal of biomedical research · 2025Article
- miR-106b-5p protects against drug-induced liver injury by targeting vimentin to stimulate liver regeneration.MedComm · 2024Article
- The Role of Vimentin in Human Corneal Fibroblast Spreading and Myofibroblast Transformation.Cells · 2024Article
- Continuous NPWT Regulates Fibrosis in Murine Diabetic Wound Healing.Pharmaceutics · 2022Article
- Unravelling Novel Roles of Salivary Exosomes in the Regulation of Human Corneal Stromal Cell Migration and Wound Healing.International journal of molecular sciences · 2022Article
- Roles of vimentin in health and disease.Genes & development · 2022Review
- Immune cells in lens injury repair and fibrosis.Experimental eye research · 2021Review
- Tackling Chronic Inflammation with Withanolide Phytochemicals-A Withaferin a Perspective.Antioxidants (Basel, Switzerland) · 2020Review
- Keratocyte mechanobiology.Experimental eye research · 2020Review
- Broad-spectrum antitumor properties of Withaferin A: a proteomic perspective.RSC medicinal chemistry · 2020Review
- Desmin deficiency is not sufficient to prevent corneal fibrosis.Experimental eye research · 2019Article
- Vimentin expression is required for the development of EMT-related renal fibrosis following unilateral ureteral obstruction in mice.American journal of physiology. Renal physiology · 2018Article
- In wound repair vimentin mediates the transition of mesenchymal leader cells to a myofibroblast phenotype.Molecular biology of the cell · 2018Article
- Vimentin on the move: new developments in cell migration.F1000Research · 2018Review
- Sustained activation of ERK1/2 MAPK in Schwann cells causes corneal neurofibroma.Journal of neuroscience research · 2017Article
- Effects of different sutures on fibrosis and wound healing in a rabbit model of corneal wounds.Experimental and therapeutic medicine · 2016Article
- Pharmacologic inhibition of reactive gliosis blocks TNF-α-mediated neuronal apoptosis.Cell death & disease · 2016Article
- Citrullination of glial intermediate filaments is an early response in retinal injury.Molecular vision · 2016Article
- Recent Advances in the Development of Antineoplastic Agents Derived from Natural Products.Drugs · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
The type III intermediate filaments (IFs) are essential cytoskeletal elements of mechanosignal transduction and serve critical roles in tissue repair. Mice genetically deficient for the IF protein vimentin (Vim(-/-)) have impaired wound healing from deficits in myofibroblast development. We report a surprising finding made in Vim(-/-) mice that corneas are protected from fibrosis and instead promote regenerative healing after traumatic alkali injury. This reparative phenotype in Vim(-/-) corneas is strikingly recapitulated by the pharmacological agent withaferin A (WFA), a small molecule that binds to vimentin and down-regulates its injury-induced expression. Attenuation of corneal fibrosis by WFA is mediated by down-regulation of ubiquitin-conjugating E3 ligase Skp2 and up-regulation of cyclin-dependent kinase inhibitors p27(Kip1) and p21(Cip1). In cell culture models, WFA exerts G(2)/M cell cycle arrest in a p27(Kip1)- and Skp2-dependent manner. Finally, by developing a highly sensitive imaging method to measure corneal opacity, we identify a novel role for desmin overexpression in corneal haze. We demonstrate that desmin down-regulation by WFA via targeting the conserved WFA-ligand binding site shared among type III IFs promotes further improvement of corneal transparency without affecting cyclin-dependent kinase inhibitor levels in Vim(-/-) mice. This dissociates a direct role for desmin in corneal cell proliferation. Taken together, our findings illuminate a previously unappreciated pathogenic role for type III IF overexpression in corneal fibrotic conditions and also validate WFA as a powerful drug lead toward anti-fibrosis therapeutic development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.