ArticleNature medicine2012
Activin-like kinase 3 is important for kidney regeneration and reversal of fibrosis.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02530359 (Pirfenidone Effect on the Recovery of Renal Function in Patients With Septic Acute Kidney Injury), which is not on this map. Cited by 126 papers.
What it found
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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.
Pirfenidone Effect on the Recovery of Renal Function in Patients With Septic Acute Kidney Injury
Who cites it
126 citing papers in PubMed, 224 citations in OpenAlex.
- Perioperative THR-184 and AKI after Cardiac Surgery.Journal of the American Society of Nephrology : JASN · 2018Trial
- Pulmonary fibroblast subsets demonstrate differentially enriched signaling pathways during fibrosis resolution and repair.JCI insight · 2026Article
- Improved protein binder design using β-pairing targeted RFdiffusion.Nature communications · 2026Article
- THR-123, a novel BMP-7 mimetic that activates Akt phosphorylation and inhibits cardiomyocyte apoptosis and inflammation, protects the heart from myocardial injury in a Rat model.Frontiers in cardiovascular medicine · 2026Article
- Kidney angiopoietin-like protein 4 regulates fibrotic responses in diabetic kidney disease.Frontiers in pharmacology · 2026Review
- Protecting kidney function: from mechanisms to therapeutic targets and traditional Chinese medicine.Renal failure · 2025Review
- Pancreatic β-cell regeneration in situ by the ALK3 agonist THR-123.Nature communications · 2025Article
- Metabolic reprogramming by endothelial ANGPTL4 depletion protects against diabetic kidney disease.bioRxiv : the preprint server for biology · 2025Article
- Autocrine GDF10 Inhibits Hepatic Stellate Cell Activation via BMPR2/ALK3 Receptor to Prevent Liver Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cardiac preservation usingFrontiers in cardiovascular medicine · 2025Article
- Runt-related transcription factors: from pathogenesis to therapeutic targets in multiple-organ fibrosis.Frontiers in cell and developmental biology · 2025Review
- Pathophysiological Mechanisms of Peritoneal Fibrosis and Peritoneal Membrane Dysfunction in Peritoneal Dialysis.International journal of molecular sciences · 2024Review
- Fatty Acid Oxidation Mediated by Malonyl-CoA Decarboxylase Represses Renal Cell Carcinoma Progression.Cancer research · 2023Article
- Small-Molecule Probes as Pharmacological Tools for the Bone Morphogenetic Protein Signaling Pathway.ACS pharmacology & translational science · 2023Review
- TGF-β Inhibitors for Therapeutic Management of Kidney Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Engineering of a Long-Acting Bone Morphogenetic Protein-7 by Fusion with Albumin for the Treatment of Renal Injury.Pharmaceutics · 2022Article
- Potential Therapeutic Role of Bone Morphogenic Protein 7 (BMP7) in the Pathogenesis of Graves' Orbitopathy.Investigative ophthalmology & visual science · 2022Article
- Uncoupling the BMP receptor antagonist function from the WNT agonist function of R-spondin 2 using the inhibitory peptide dendrimer RWThe Journal of biological chemistry · 2022Article
- miR-29c Inhibits Renal Interstitial Fibrotic Proliferative Properties through PI3K-AKT Pathway.Applied bionics and biomechanics · 2022Article
- A Process for the Design and Development of Novel Bone Morphogenetic Protein-7 (BMP-7) Mimetics With an Example: THR-184.Frontiers in pharmacology · 2022Article
66 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Molecules associated with the transforming growth factor β (TGF-β) superfamily, such as bone morphogenic proteins (BMPs) and TGF-β, are key regulators of inflammation, apoptosis and cellular transitions. Here we show that the BMP receptor activin-like kinase 3 (Alk3) is elevated early in diseased kidneys after injury. We also found that its deletion in the tubular epithelium leads to enhanced TGF-β1-Smad family member 3 (Smad3) signaling, epithelial damage and fibrosis, suggesting a protective role for Alk3-mediated signaling in the kidney. A structure-function analysis of the BMP-Alk3-BMP receptor, type 2 (BMPR2) ligand-receptor complex, along with synthetic organic chemistry, led us to construct a library of small peptide agonists of BMP signaling that function through the Alk3 receptor. One such peptide agonist, THR-123, suppressed inflammation, apoptosis and the epithelial-to-mesenchymal transition program and reversed established fibrosis in five mouse models of acute and chronic renal injury. THR-123 acts specifically through Alk3 signaling, as mice with a targeted deletion for Alk3 in their tubular epithelium did not respond to therapy with THR-123. Combining THR-123 and the angiotensin-converting enzyme inhibitor captopril had an additive therapeutic benefit in controlling renal fibrosis. Our studies show that BMP signaling agonists constitute a new line of therapeutic agents with potential utility in the clinic to induce regeneration, repair and reverse established fibrosis.
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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.