ArticleCell proliferation2023
TGF-β-induced PI3K/AKT/mTOR pathway controls myofibroblast differentiation and secretory phenotype of valvular interstitial cells through the modulation of cellular senescence in a naturally occurring in vitro canine model of myxomatous mitral valve disease.
Article in Cell proliferation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 60 citations in OpenAlex.
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- Nano-enabled natriuretic peptide therapy in post-myocardial infarction heart failure: from functional NP deficiency to dual-axis (cGMP-dependent and -independent) cardioprotection.Internal and emergency medicine · 2026Review
- Beyond EMT: Mesenchymal drift as an emerging driver of stromal-immune reprogramming in prostate cancer.iScience · 2026Review
- Scleral Postn Drives Myopia via Promoting Myofibroblast Transdifferentiation.Investigative ophthalmology & visual science · 2026Article
- ITGA1 promotes osteogenic differentiation of human periodontal ligament stem cells via FAK-mediated PI3K-Akt activation.Stem cell research & therapy · 2026Article
- Prevalence of rs850683722 Variant and Its Influence on the Course of Myxomatous Mitral Valve Disease in 105 Cavalier King Charles Spaniel Dogs in the Polish Population.Animals : an open access journal from MDPI · 2026Article
- Multicellular senescence programs in the aged heart.Journal of molecular and cellular cardiology plus · 2026Review
- AGEs derived from high-sugar diets induce functional impairment of odontogenic stem cells via RAGE-mediated endoplasmic reticulum stress.Histochemistry and cell biology · 2026Article
- PHGDH Orchestrates Cell Cycle Progression to Drive Cardiomyocyte Proliferation and Myocardial Regeneration via TGF-β/Smad Signalling Pathway.Cell proliferation · 2026Article
- NR4A1 mediates chemotherapy‑induced senescence via the PI3K/AKT pathway in gastric cancer cells.Oncology reports · 2026Article
- Tadehagi triquetrum aqueous extract ameliorates diabetic kidney disease through mitigating epithelial senescence via the PTEN/AKT/mTOR signaling pathway.Chinese medicine · 2026Article
- Transforming Gastric Biopsy Diagnostics: Integrating Omics Technologies and Artificial Intelligence.Biomedicines · 2026Article
- Interconnected Pathways and Therapeutic Implications for Cardiovascular Aging and Diseases.JACC. Asia · 2026Review
- Selective phosphoinositide 3-kinase inhibitors and implication in diabetic retinopathy as pharmacological tools.Frontiers in pharmacology · 2026Review
- Marine-Derived Quinolinone CHNQD-00603 Triggers Autophagy via Suppressing the AKT/ERK/mTOR Pathway to Reverse Senescence and Restore Osteogenic Potential in Bone Marrow Mesenchymal Stem Cells.Current protein & peptide science · 2026Article
- Fisetin promotes skin wound healing and inhibits pathological scar formation through modulation of the PI3K/Akt/TGF-β1 signaling axis.Frontiers in pharmacology · 2026Article
- TRIM3 exacerbates chondrocyte apoptosis through suppression of AKT/mTOR signaling pathway in osteoarthritis.Journal of orthopaedic surgery and research · 2025Article
- Dapagliflozin inhibits TGF-β-induced transdifferentiation of valvular interstitial cells and mitral valvular degeneration.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Targeted nanodelivery strategies for atrial fibrillation: concomitant targeting of fibrosis suppression and electrical conduction restoration through advanced nanobiotechnology.Journal of nanobiotechnology · 2025Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
PI3K/AKT/mTOR signalling contributes to several cardiovascular disorders. The aim of this study was to examine the PI3K/AKT/mTOR pathway in myxomatous mitral valve disease (MMVD). Double-immunofluorescence examined expression of PI3K and TGF-β1 in canine valves. Valve interstitial cells (VICs) from healthy or MMVD dogs were isolated and characterized. Healthy quiescent VICs (qVICs) were treated with TGF-β1 and SC-79 to induce activated myofibroblast phenotypes (aVICs). Diseased valve-derived aVICs were treated with PI3K antagonists and expression of RPS6KB1 (encoding p70 S6K) was modulated using siRNA and gene overexpression. SA-β-gal and TUNEL staining were used to identify cell senescence and apoptosis, and qPCR and ELISA to examine for senescence-associated secretory phenotype. Protein immunoblotting was used to examine expression of phosphorylated and total proteins. TGF-β1 and PI3K are highly expressed in mitral valve tissues. Activation of PI3K/AKT/mTOR and increased expression of TGF-β are found in aVICs. TGF-β transitions qVICs to aVICs by upregulation of PI3K/AKT/mTOR. Antagonism of PI3K/AKT/mTOR reverses aVIC myofibroblast transition by inhibiting senescence and promoting autophagy. Upregulation of mTOR/S6K induces transformation of senescent aVICs, with reduced capacity for apoptosis and autophagy. Selective knockdown of p70 S6K reverses cell transition by attenuating cell senescence, inhibiting apoptosis and improving autophagy. TGF-β-induced PI3K/AKT/mTOR signalling contributes to MMVD pathogenesis and plays crucial roles in the regulation of myofibroblast differentiation, apoptosis, autophagy and senescence in MMVD.
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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.