ArticleArthritis research & therapy2018
Blockade of TGF-β/Smad signaling by the small compound HPH-15 ameliorates experimental skin fibrosis.
Article in Arthritis research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Macrophages and TGFB signaling regulate fibrosis in theAmerican journal of physiology. Renal physiology · 2026Article
- Cuproptosis-related gene TMPO affects the healing of diabetic foot ulcers through TGF-β/Smad signaling pathway.iScience · 2025Article
- Mechanisms of prostatic inflammation-mediated male lower urinary tract symptoms.American journal of clinical and experimental urology · 2025Review
- An antifibrotic compound that ameliorates hyperglycaemia and fat accumulation in cell and HFD mouse models.Diabetologia · 2024Article
- Antioxidant therapy against TGF-β/SMAD pathway involved in organ fibrosis.Journal of cellular and molecular medicine · 2024Review
- WDR74 facilitates TGF-β/Smad pathway activation to promote M2 macrophage polarization and diabetic foot ulcer wound healing in mice.Cell biology and toxicology · 2023Article
- M2 macrophage polarization in systemic sclerosis fibrosis: pathogenic mechanisms and therapeutic effects.Heliyon · 2023Review
- Macrophage polarization in tissue fibrosis.PeerJ · 2023Review
- Novel Inhibitor for Downstream Targeting of Transforming Growth Factor-β Signaling to Suppress Epithelial to Mesenchymal Transition and Cell Migration.International journal of molecular sciences · 2022Article
- The compound LG283 inhibits bleomycin-induced skin fibrosis via antagonizing TGF-β signaling.Arthritis research & therapy · 2022Article
- FermentedFood science & nutrition · 2022Article
- Butyrate Improves Skin/Lung Fibrosis and Intestinal Dysbiosis in Bleomycin-Induced Mouse Models.International journal of molecular sciences · 2021Article
- Candidate rejuvenating factor GDF11 and tissue fibrosis: friend or foe?GeroScience · 2020Review
- AAV1.SERCA2a Gene Therapy Reverses Pulmonary Fibrosis by Blocking the STAT3/FOXM1 Pathway and Promoting the SNON/SKI Axis.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- LMP1 Up-regulates Calreticulin to Induce Epithelial-mesenchymal Transition via TGF-β/Smad3/NRP1 Pathway in Nasopharyngeal Carcinoma Cells.Journal of Cancer · 2020Article
- DZ2002 ameliorates fibrosis, inflammation, and vasculopathy in experimental systemic sclerosis models.Arthritis research & therapy · 2019Article
- Antifibrotic effects of 2-carba cyclic phosphatidic acid (2ccPA) in systemic sclerosis: contribution to the novel treatment.Arthritis research & therapy · 2019Article
- Total flavone ofWorld journal of gastroenterology · 2018Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundTransforming growth factor-β (TGF-β)/Smad signaling is well known to play a critical role in the pathogenesis of systemic sclerosis (SSc). We previously developed an artificial molecule, the histidine-pyridine-histidine ligand derivative HPH-15, which may have an antifibrotic effect. The purpose of the present study was to clarify the effects of this drug in human skin fibroblasts and in a preclinical model of SSc.
methodsThe effects of HPH-15 on expression of extracellular matrix components and TGF-β signaling in human dermal fibroblasts were analyzed. The antifibrotic properties of HPH-15 and its mechanisms were also examined in a bleomycin-induced skin fibrosis mouse model.
resultsHPH-15 suppressed the TGF-β-induced phosphorylation of Smad3 and inhibited the expression of collagen I, fibronectin 1, connective tissue growth factor, and α-smooth muscle actin induced by TGF-β in cultured human skin fibroblasts. In the bleomycin-induced skin fibrosis model, oral administration of HPH-15 protected against the development of skin fibrosis and ameliorated established skin fibrosis. Additionally, HPH-15 suppressed the phosphorylation of Smad3 in various cells, including macrophages in the bleomycin-injected skin. Further, in the treated mice, dermal infiltration of proinflammatory macrophages (CD11b
conclusionsHPH-15 may inhibit skin fibrosis by inhibiting the phosphorylation of Smad3 in dermal fibroblasts and possibly in macrophages. Our results demonstrate several positive qualities of HPH-15, including oral bioavailability, a good safety profile, and therapeutic effectiveness. Thus, this TGF-β/Smad inhibitor is a potential candidate therapeutic for SSc clinical trials.
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