ArticleThe Journal of clinical investigation2017
Cell-penetrating peptides selectively targeting SMAD3 inhibit profibrotic TGF-β signaling.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Antagonistic SMAD2/3 control of TIMP-1, VEGF-A, and hypoxia signaling in myofibroblasts shapes histotype-specific angiogenesis in lung cancer.Cell death & disease · 2026Article
- Therapeutic Targets for Myocardial Fibrosis: A Comprehensive Review of Current and Emerging Approaches.Cardiovascular & hematological disorders drug targets · 2026Review
- Cathepsin K Aggravates Pulmonary Fibrosis Through Promoting Fibroblast Glutamine Metabolism and Collagen Synthesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mechanisms of extracellular vesicle uptake and implications for the design of cancer therapeutics.Journal of extracellular biology · 2024Review
- Biogenesis and Function of circRNAs in Pulmonary Fibrosis.Current gene therapy · 2024Review
- A cell-penetrating PHLPP peptide improves cardiac arrest survival in murine and swine models.The Journal of clinical investigation · 2023Article
- Sorting nexins: role in the regulation of blood pressure.The FEBS journal · 2023Review
- Article
- Review
- E4 engages uPAR and enolase-1 and activates urokinase to exert antifibrotic effects.JCI insight · 2021Article
- Targeting Intercellular Communication in the Bone Microenvironment to Prevent Disseminated Tumor Cell Escape from Dormancy and Bone Metastatic Tumor Growth.International journal of molecular sciences · 2021Review
- Long non-coding RNAs: Promising new targets in pulmonary fibrosis.The journal of gene medicine · 2021Review
- The Role of TGF-Evidence-based complementary and alternative medicine : eCAM · 2021Review
- Associations between the concentrations of CD68, TGF-β1, renal injury index and prognosis in glomerular diseases.Experimental and therapeutic medicine · 2020Article
- Low-Dose Ionizing Radiation Modulates Microglia Phenotypes in the Models of Alzheimer's Disease.International journal of molecular sciences · 2020Article
- IPF pathogenesis is dependent upon TGFβ induction of IGF-1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- A Perspective on the Development of TGF-β Inhibitors for Cancer Treatment.Biomolecules · 2019Review
- A Long Noncoding RNA links TGF-β Signaling in Lung Fibrosis.American journal of respiratory and critical care medicine · 2019Article
- The cell-penetrating FOXM1 N-terminus (M1-138) demonstrates potent inhibitory effects on cancer cells by targeting FOXM1 and FOXM1-interacting factor SMAD3.Theranostics · 2019Article
- TGF-β and the Tissue Microenvironment: Relevance in Fibrosis and Cancer.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
TGF-β is considered a master switch in the pathogenesis of organ fibrosis. The primary mediators of this activity are the SMAD proteins, particularly SMAD3. In the current study, we have developed a cell-penetrating peptide (CPP) conjugate of the HIV TAT protein that is fused to an aminoterminal sequence of sorting nexin 9 (SNX9), which was previously shown to bind phosphorylated SMAD3 (pSMAD3). We determined that specifically preventing the nuclear import of pSMAD3 using the TAT-SNX9 peptide inhibited profibrotic TGF-β activity in murine cells and human lung fibroblasts as well as in vivo with no demonstrable toxicity. TGF-β signaling mediated by pSMAD2, bone morphogenetic protein 4 (BMP4), EGF, or PDGF was unaffected by the TAT-SNX9 peptide. Furthermore, while the TAT-SNX9 peptide prevented TGF-β's profibrotic activity in vitro as well as in 2 murine treatment models of pulmonary fibrosis, a 3-amino acid point mutant that was unable to bind pSMAD3 proved ineffective. These findings indicate that specifically targeting pSMAD3 can ameliorate both the direct and indirect fibroproliferative actions of TGF-β.
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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.