ArticleTherapeutic advances in chronic disease2019
Combined melatonin and poricoic acid A inhibits renal fibrosis through modulating the interaction of Smad3 and β-catenin pathway in AKI-to-CKD continuum.
Article in Therapeutic advances in chronic disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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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
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- TGF-β/Smad Signaling Pathway in Tubulointerstitial Fibrosis.Frontiers in pharmacology · 2022Pooled it
- Protective Effect of Melatonin for Renal Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis.Frontiers in physiology · 2021Pooled it
- Circadian Influences on Chronic Kidney Disease Progression: Molecular Signaling Pathways of Melatonin and Their Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Transition from acute kidney injury to chronic kidney disease: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Role of the TGF‑β/Smad signaling pathway in the transition from acute kidney injury to chronic kidney disease (Review).International journal of molecular medicine · 2025Review
- CCN5 negatively regulates TGF-β-induced endometriosis associated fibrosis through Wnt/β-catenin signaling via Smad3-dependent mechanism.Journal of translational medicine · 2025Article
- Mechanisms of Acute Kidney Injury-Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities.Biomolecules · 2025Review
- Poria cocos: traditional uses, triterpenoid components and their renoprotective pharmacology.Acta pharmacologica Sinica · 2025Review
- Natural products in traditional Chinese medicine for renal fibrosis: a comprehensive review.Frontiers in pharmacology · 2025Review
- A Natural Small Molecule Mitigates Kidney Fibrosis by Targeting Cdc42-mediated GSK-3β/β-catenin Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Therapeutic potential of melatonin in targeting molecular pathways of organ fibrosis.Pharmacological reports : PR · 2024Review
- Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Effect of QingreHuoxue formula on Th17 cells and Tregs in mice with idiopathic membranous nephropathy.American journal of translational research · 2024Article
- Poricoic acid A attenuates renal fibrosis by inhibiting endoplasmic reticulum stress-mediated apoptosis.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- Hexarelin alleviates apoptosis on ischemic acute kidney injury via MDM2/p53 pathway.European journal of medical research · 2023Article
- The Cactus (Antioxidants (Basel, Switzerland) · 2023Article
- Pharmacological Mechanisms and Clinical Applications of Curcumin: Update.Aging and disease · 2023Review
- Poricoic acid A suppresses renal fibroblast activation and interstitial fibrosis in UUO rats via upregulating Sirt3 and promoting β-catenin K49 deacetylation.Acta pharmacologica Sinica · 2023Article
- NFAT inhibitor 11R-VIVIT ameliorates mouse renal fibrosis after ischemia-reperfusion-induced acute kidney injury.Acta pharmacologica Sinica · 2022Article
- Traditional Chinese Medicine in the Treatment of Chronic Kidney Diseases: Theories, Applications, and Mechanisms.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcute kidney injury (AKI) is one of the major risk factors for progression to chronic kidney disease (CKD) and renal fibrosis. However, effective therapies remain poorly understood. Here, we examined the renoprotective effects of melatonin and poricoic acid A (PAA) isolated from the surface layer of
methodsWestern blot and immunohistochemical staining were used to examine protein expression, while qRT-PCR was used to examine mRNA expression. Coimmunoprecipitation, chromatin immunoprecipitation, RNA interference, and luciferase reporter gene analysis were employed to explore the mechanisms of PAA and melatonin's renoprotective effects.
resultsPAA and combined therapy exhibited renoprotective and antifibrotic effects, but the underlying mechanisms were different during AKI-to-CKD continuum. Melatonin suppressed Smad-dependent and Smad-independent pathways, while PAA selectively inhibited Smad3 phosphorylation through distrupting the interactions of Smad3 with TGFβRI and SARA. Further studies demonstrated that the inhibitory effects of melatonin and PAA were partially depended on Smad3, especially PAA. Melatonin and PAA also inhibited the Wnt/β-catenin pathway and its profibrotic downstream targets, and PAA performed better. We further determined that IRI induced a nuclear Smad3/β-catenin complex, while melatonin and PAA disturbed the interaction of Smad3 and β-catenin, and supplementing with PAA could enhance the inhibitory effects of melatonin on the TGF-β/Smad and Wnt/β-catenin pathways.
conclusionsCombined melatonin and PAA provides a promising therapeutic strategy to treat renal fibrosis during the AKI-to-CKD continuum.
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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.