The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Preclinical Study of Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Hypertrophic Scars in a Common Marmoset Primate Model
Open accessAbstract
We report a preclinical study of a pyrrole-imidazole (PI) polyamide that targets the human transforming growth factor (hTGF)-β1 gene as a novel transcriptional gene silencer in a common marmoset primate model. We designed and then synthesized PI polyamides to target the hTGF-β1 promoter. We examined effects of seven PI polyamides (GB1101-1107) on the expression of hTGF-β1 mRNA stimulated with phorbol 12-myristate 13-acetate (PMA) in human vascular smooth muscle cells. GB1101, GB1105 and GB1106 significantly inhibited hTGF-β1 mRNA expression. We examined GB1101 as a PI polyamide to hTGF-β1 for hypertrophic scars in marmosets in vivo. Injection of GB1101 completely inhibited hypertrophic scar formation at 35 days post-incision and inhibited cellular infiltration, TGF-β1 and vimentin staining, and epidermal thickness. Mismatch polyamide did not affect hypertrophic scarring or histological changes. Epidermis was significantly thinner with GB1101 than with water and mismatch PI polyamides. We developed the PI polyamides for practical ointment medicines for the treatment of hypertrophic scars. FITC-labeled GB1101 with solbase most efficiently distributed in the nuclei of epidermal keratinocytes, completely suppressed hypertropic scarring at 42 days after incision, and considerably inhibited epidermal thickness and vimentin-positive fibroblasts. PI polyamides targeting hTGF-β1 promoter with solbase ointment will be practical medicines for treating hypertrophic scars after surgical operations and skin burns.
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These inhibitors may also inhibit other kinases, such as p38 MAPK.
“and may also inhibit other kinases, such as p38 MAPK292,294.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [292]
Galunisertib is a well-studied small molecule inhibitor of TGF-β receptor kinases.
“One class, exemplified by galunisertib (LY2157299; developed by Eli Lilly) as a well-studied therapeutic291,292 consists of small molecule inhibitors of TGF-β receptor kinases.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [292]
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TGFβ biology in cancer progression and immunotherapy
Derynck, R., Turley, S. J., & Akhurst, R. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0403-1 · Cited by 944
Metadata
- Authors
- Igarashi, J., Fukuda, N., Inoue, T., Nakai, S., Saito, K., Fujiwara, K., Matsuda, H., Ueno, T., Matsumoto, Y., Watanabe, T., Nagase, H., Bando, T., Sugiyama, H., Itoh, T., & Soma, M.
- Affiliations
- Nihon University (JP)
- Central Institute for Experimental Animals (JP)
- Chiba Cancer Center Research Institute (JP)
- Kyoto University (JP)
- Corresponding author
- Fukuda, Noboru
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-05-04
- Volume
- 10
- Issue
- 5
- Pages
- e0125295
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4418757
- OpenAlex
- W254155429
- Cited by
- 39
- References
- 24
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 2 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 3 · 2016: 2
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
- Funders
- Nihon University
- Ministry of Education, Culture, Sports, Science and Technology (2009-2013)
- Japan Society for the Promotion of Science (24225005, 24310155)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Keywords
- pyrrole-imidazole polyamides, gene silencing, hypertrophic scars, Callithrix jacchus, transcriptional repression, vascular smooth muscle cells, epidermal thickness, keratinocytes, burn scars, postoperative scarring
- MeSH terms
- Animals, Base Sequence, Binding Sites, Callithrix, Disease Models, Animal, Humans, Imidazoles, Injections, Male, Molecular Sequence Data, Nylons, Ointments, Promoter Regions, Genetic, Pyrroles, RNA, Messenger, Cicatrix, Hypertrophic, Gene Targeting, Gene Silencing, Transforming Growth Factor beta1
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