- |||||||||| Journal: Legumain is a paracrine regulator of osteoblast differentiation and mediates the inhibitory effect of TGF-?1 on osteoblast maturation. (Pubmed Central) - Oct 4, 2024
Our findings reveal that TGF-?1 inhibits osteoblast maturation by stimulating secretion and activity of endogenous legumain, as well as enhancing internalization and activation of extracellular prolegumain. Therefore, our study provides a deeper understanding of the complex regulation of osteoblastogenesis and unveils a novel TGF-?1-legumain axis in regulation of osteoblast maturation, offering novel insights for possible therapeutic interventions related to bone diseases associated with aberrant TGF-?1 signaling.
- |||||||||| Anti-fibrotic effects of the sirt6-activator mdl-800 in cardiac stromal cells (Station 9 - Research Gateway) - May 14, 2024 - Abstract #ESC2024ESC_5785;
Therefore, it holds therapeutic potential for CRS, and a synergistic effect can be expected when loaded with CRS treatment drugs. MDL-800 treatment in CSCs is associated with a dose-dependent reduction of TGFb1-induced fibrotic markers and to increased levels of the autophagy marker, suggesting its potential use as an anti-fibrotic molecule for the heart.
- |||||||||| galunisertib (LY2157299) / Eli Lilly
Journal, PD(L)-1 Biomarker, IO biomarker: MicroRNA-431-5p inhibits angiogenesis, lymphangiogenesis, and lymph node metastasis by affecting TGF-?1/SMAD2/3 signaling via ZEB1 in gastric cancer. (Pubmed Central) - Apr 24, 2024 Additionally, miR-431-5p enhances the efficacy of anti-PD1 treatment, particularly when combined with galunisertib, anti-PD1 treatment showing a synergistic effect in inhibiting GC progression in C57BL/6 mice. Collectively, these findings suggest that miR-431-5p may modulate the TGF-?1/SMAD2/3 pathways by targeting ZEB1 to impede GC progression, angiogenesis, and lymphangiogenesis, making it a promising therapeutic target for GC management.
- |||||||||| Review, Journal: The involvement of the Wnt/?-catenin signaling cascade in fibrosis progression and its therapeutic targeting by relaxin. (Pubmed Central) - Mar 16, 2024
It also outlines the anti-fibrotic and related signal transduction mechanisms of the hormone, relaxin, that are mediated via its negative modulation of TGF-?1 and Wnt/?-catenin signaling, but through the promotion of Wnt/?-catenin activity in acute disease settings. Collectively, this highlights that the crosstalk between TGF-?1 signal transduction and the Wnt/?-catenin cascade may provide a therapeutic target that can be exploited to broadly treat and reverse established fibrosis.
- |||||||||| Preclinical, Journal: Periodontal ligament-associated protein-1 promotes osteoclastogenesis in mice by modulating TGF-?1/Smad1 pathway. (Pubmed Central) - Mar 4, 2024
Collectively, this highlights that the crosstalk between TGF-?1 signal transduction and the Wnt/?-catenin cascade may provide a therapeutic target that can be exploited to broadly treat and reverse established fibrosis. This study revealed that the knockout of PLAP-1 inhibits osteoclast differentiation and decreases alveolar bone resorption through the TGF-?1/Smad1 signaling pathway, which could serve as an innovative target for the prevention and treatment of periodontitis.
- |||||||||| Journal: Myocardial fibrosis induced by nonylphenol and its regulatory effect on the TGF-?1/LIMK1 signaling pathway. (Pubmed Central) - Feb 26, 2024
Taken together, our findings are the first to demonstrate the effectiveness of pharmacological sGC stimulation in counteracting conjunctival fibroblast-to-myofibroblast transition, thus providing a promising scientific background to further explore the feasibility of sGC stimulators as potential new adjuvant therapeutic compounds to treat conjunctival fibrotic conditions. We here provide the first evidence that perinatal NP exposure causes myocardial fibrosis in growing male rat pups and reveal the molecular mechanism and functional role of the TGF-?1/LIMK1 signaling pathway in this process.
- |||||||||| Visudyne (verteporfin) / Novartis
Journal: Development and Verification of a Novel Three-Dimensional Aqueous Outflow Model for High-Throughput Drug Screening. (Pubmed Central) - Feb 23, 2024 This study (1) introduces a novel high-throughput screening platform for testing potential anti-fibrotic compounds and (2) assesses the clinical viability of modulating the transforming growth factor beta-SMAD2/3 pathway as a key contributor to post-operative outflow reduction, using the signal transduction inhibitor verteporfin...These demonstrate modulation of the aforementioned pathway as a potential avenue for addressing post-operative changes and reductions in filtration bleb outflow capacity. Furthermore, the establishment of a high-throughput screening platform offers a valuable pre-animal testing tool for investigating potential compounds to facilitate surgical wound healing.
- |||||||||| Journal: Sfrp1 inhibits lung fibroblast invasion during transition to injury induced myofibroblasts. (Pubmed Central) - Jan 11, 2024
Our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies SFRP1 as a modulator of TGF?1-driven fibroblast phenotypes in fibrogenesis. These findings are relevant in the context of therapeutic interventions that aim at limiting or reversing fibroblast foci formation.
- |||||||||| Journal: TREM2 regulates microglial lipid droplet formation and represses post-ischemic brain injury. (Pubmed Central) - Dec 2, 2023
TREM2 may play a direct role in the regulation of inflammation and also exert an influence on the post-ischemic inflammation and the stroke pathology progression via regulation of lipid metabolism processes. Thus, underscoring the therapeutic potential of TREM2 agonists in ischemic stroke and making TREM2 an attractive new clinical target for the treatment of ischemic stroke and other inflammation-related diseases.
- |||||||||| dorsomorphin (Compound C) / EMD Serono
Biomarker, Journal, Tumor cell: GLIS3, a novel prognostic indicator of gastric adenocarcinoma, contributes to the malignant biological behaviors of tumor cells via modulating TGF-?1/TGF?R1/Smad1/5 signaling pathway. (Pubmed Central) - Sep 11, 2023 Overexpressed GLIS3 promoted proliferation, migration, invasion, TGF-?1 expression and Smad1/5 phosphorylation in GAC cells, with SB505124 reversing the effects of overexpressed GLIS3 on proliferation, migration, invasion and Smad1/5 phosphorylation whereas dorsomorphin exhibiting no influence on GLIS3-induced effects. GLIS3 facilitated the malignant phenotype of GAC cells via regulating TGF-?1/TGF?R1/Smad1/5 pathway, which may be a novel prognostic indicator of GAC and provided a target for GAC treatment.
- |||||||||| bleomycin / Generic mfg.
Journal: Investigating the role of platelets and platelet-derived transforming growth factor-? in idiopathic pulmonary fibrosis. (Pubmed Central) - Aug 29, 2023 To study whether platelet-derived TGF?1 modulates pulmonary fibrosis (PF), mice with a targeted deletion of TGF?1 in megakaryocytes and platelets (TGF?1.PF4-Cre) were used in the well-characterized bleomycin-induced pulmonary fibrosis (PF) animal model...Our results demonstrate for the first-time that platelet-derived TGF?1 does not significantly mediate inflammation or fibrosis in a PF animal model. Furthermore, our human studies revealed blood platelet counts do not consistently predict mortality in IPF but other platelet-derived mediators, such as CCL5, may promote neutrophil recruitment and human IPF.
- |||||||||| Review, Journal: The immunity modulation of transforming growth factor-? in malaria and other pathological process. (Pubmed Central) - Aug 25, 2023
maintains a dynamic balance between anti-inflammation and pro-inflammation in malaria immunity by acting as an anti-inflammatory factor when inflammation levels are too high and as a pro-inflammatory factor when inflammation levels are deficient. Such information could be of relevance to the design of urgently needed vaccines and medications to meet the emerging risks associated with the increasing spread of malaria and the development of drug resistance.
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