ArticleScientific reports2016
Blocking protein phosphatase 2A signaling prevents endothelial-to-mesenchymal transition and renal fibrosis: a peptide-based drug therapy.
Article in Scientific reports, 2016. 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, 36 citations in OpenAlex.
- Nitration in cancer signaling.Redox biology · 2026Review
- Endothelial remodeling in osteosarcomas: insights from patient samples and in vitro studies.American journal of cancer research · 2025Article
- Role of perivascular cells in kidney homeostasis, inflammation, repair and fibrosis.Nature reviews. Nephrology · 2023Review
- PP2A phosphatase inhibition is anti-fibrotic through Ser77 phosphorylation-mediated ARNT/ARNT homodimer formation.Scientific reports · 2021Article
- Role of protein phosphatase 2A in kidney disease (Review).Experimental and therapeutic medicine · 2021Review
- PP2Acα promotes macrophage accumulation and activation to exacerbate tubular cell death and kidney fibrosis through activating Rap1 and TNFα production.Cell death and differentiation · 2021Article
- The renal microcirculation in chronic kidney disease: novel diagnostic methods and therapeutic perspectives.Cell & bioscience · 2021Review
- Endothelial-to-mesenchymal transition compromises vascular integrity to induce Myc-mediated metabolic reprogramming in kidney fibrosis.Science signaling · 2020Article
- Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression.Redox biology · 2019Review
- Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases.Physiological reviews · 2019Review
- The therapeutic potential of targeting the endothelial-to-mesenchymal transition.Angiogenesis · 2019Review
- Klotho Inhibits Unilateral Ureteral Obstruction-Induced Endothelial-to-Mesenchymal TransitionFrontiers in pharmacology · 2019Article
- Simvastatin reduces TGF-β1-induced SMAD2/3-dependent human ventricular fibroblasts differentiation: Role of protein phosphatase activation.International journal of cardiology · 2018Article
- Epoxyeicosatrienoic acid activation moderates endothelial mesenchymal transition to reduce obstructive nephropathy.Kidney research and clinical practice · 2017Article
- TGF-β-Induced Endothelial-Mesenchymal Transition in Fibrotic Diseases.International journal of molecular sciences · 2017Review
- Endothelial Hey2 deletion reduces endothelial-to-mesenchymal transition and mitigates radiation proctitis in mice.Scientific reports · 2017Article
- Puerarin Protects against Cardiac Fibrosis Associated with the Inhibition of TGF-PPAR research · 2017Article
- Lovastatin Alleviates Endothelial-to-Mesenchymal Transition in Glomeruli via Suppression of Oxidative Stress and TGF-β1 Signaling.Frontiers in pharmacology · 2017Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial-to-mesenchymal transition (EndMT) contributes to the emergence of fibroblasts and plays a significant role in renal interstitial fibrosis. Protein phosphatase 2A (PP2A) is a major serine/threonine protein phosphatase in eukaryotic cells and regulates many signaling pathways. However, the significance of PP2A in EndMT is poorly understood. In present study, the role of PP2A in EndMT was evaluated. We demonstrated that PP2A activated in endothelial cells (EC) during their EndMT phenotype acquisition and in the mouse model of obstructive nephropathy (i.e., UUO). Inhibition of PP2A activity by its specific inhibitor prevented EC undergoing EndMT. Importantly, PP2A activation was dependent on tyrosine nitration at 127 in the catalytic subunit of PP2A (PP2Ac). Our renal-protective strategy was to block tyrosine127 nitration to inhibit PP2A activation by using a mimic peptide derived from PP2Ac conjugating a cell penetrating peptide (CPP: TAT), termed TAT-Y127WT. Pretreatment with TAT-Y127WT was able to prevent TGF-β1-induced EndMT. Administration of the peptide to UUO mice significantly ameliorated renal EndMT level, with preserved density of peritubular capillaries and reduction in extracellular matrix deposition. Taken together, these results suggest that inhibiting PP2Ac nitration using a mimic peptide is a potential preventive strategy for EndMT in renal fibrosis.
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