ArticleBiomolecules2019
All-Trans Retinoic Acid Attenuates Fibrotic Processes by Downregulating TGF-β1/Smad3 in Early Diabetic Nephropathy.
Article in Biomolecules, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 40 citations in OpenAlex.
- Review
- Systems pharmacology, structural modeling, and experimental validation reveal retinoic acid as a modulator of immune-fibrotic networks in chronic kidney disease.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Multi-omics and machine learning reveal LYZ and ISG15 as diagnostic and therapeutic targets in autoimmune-mediated chronic kidney disease.Frontiers in immunology · 2026Article
- Deconvolution of molecular mechanisms in di-n-butyl phthalate/mono-n-butyl phthalate induced diabetic kidney disease by integrated machine learning and molecular docking.BMC nephrology · 2025Article
- RXRActa pharmaceutica Sinica. B · 2025Article
- METTL3 Potentiates M2 Macrophage-Driven MMT to Aggravate Renal Allograft Fibrosis via the TGF-β1/Smad3 Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Diabetic kidney disease: from pathogenesis to multimodal therapy-current evidence and future directions.Frontiers in medicine · 2025Review
- Retinoic acid receptor α activity in proximal tubules prevents kidney injury and fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Retinoic Acid Receptor Is a Novel Therapeutic Target for Postoperative Cognitive Dysfunction.Pharmaceutics · 2023Article
- Pathway from Acute Kidney Injury to Chronic Kidney Disease: Molecules Involved in Renal Fibrosis.International journal of molecular sciences · 2023Review
- Vitamin A and retinoid signaling in the kidneys.Pharmacology & therapeutics · 2023Review
- Metabolite Profiling of the Gut-Renal-Cerebral Axis Reveals a Particular Pattern in Early Diabetic Kidney Disease in T2DM Patients.International journal of molecular sciences · 2023Article
- Retinoic acid associates with mortality of patients on long-term hemodialysis.Renal failure · 2022Article
- Renal Proximal Tubular Cells: A New Site for Targeted Delivery Therapy of Diabetic Kidney Disease.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Resveratrol in Treating Diabetes and Its Cardiovascular Complications: A Review of Its Mechanisms of Action.Antioxidants (Basel, Switzerland) · 2022Review
- Dysregulated Retinoic Acid Signaling in the Pathogenesis of Pseudoexfoliation Syndrome.International journal of molecular sciences · 2022Article
- Synthetic Retinoids Beyond Cancer Therapy.Annual review of pharmacology and toxicology · 2022Review
- Smad3 Signatures in Renal Inflammation and Fibrosis.International journal of biological sciences · 2022Review
- Molecular mechanisms of TGFβ-mediated EMT of retinal pigment epithelium in subretinal fibrosis of age-related macular degeneration.Frontiers in ophthalmology · 2022Review
- A New Prospect for the Treatment of Nephrotic Syndrome Based on Network Pharmacology Analysis.Current research in physiology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic nephropathy (DN) involves damage associated to hyperglycemia and oxidative stress. Renal fibrosis is a major pathologic feature of DN. The aim of this study was to evaluate anti-fibrogenic and renoprotective effects of all-trans retinoic acid (ATRA) in isolated glomeruli and proximal tubules of diabetic rats. Diabetes was induced by single injection of streptozotocin (STZ, 60 mg/Kg). ATRA (1 mg/Kg) was administered daily by gavage, from days 3-21 after STZ injection. ATRA attenuated kidney injury through the reduction of proteinuria, renal hypertrophy, increase in natriuresis, as well as early markers of damage such as β2-microglobulin, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL). The following parameters increased: macrophage infiltration, localization of alpha-smooth muscle actin (αSMA)-positive cells in renal tissue, and pro-fibrotic proteins such as transforming growth factor-β (TGF-β1), laminin beta 1 (LAM-β1), and collagens IV and I. Remarkably, ATRA treatment ameliorated these alterations and attenuated expression and nuclear translocation of Smad3, with increment of glomerular and tubular Smad7. The diabetic condition decreased expression of retinoic acid receptor alpha (RAR-α) through phosphorylation in serine residues mediated by the activation of c-Jun N-terminal kinase (JNK). ATRA administration restored the expression of RAR-α and inhibited direct interactions of JNK/RAR-α. ATRA prevented fibrogenesis through down-regulation of TGF-β1/Smad3 signaling.
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Registered trials
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