ArticleNature chemical biology2025
A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Rhein from a traditional herbal formula attenuates hepatic fibrosis via ALDH1A3-mediated retinoic acid metabolism.Chinese medicine · 2026Article
- Molecular imaging-guided discovery of a potent natural FAPα inhibitor for liver fibrosis therapy.Nature communications · 2026Article
- Saikosaponin B1 alleviates hepatic fibrosis by targeting the LDHA-MCT1/4 axis to inhibit lactate-driven profibrogenic signaling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- APOL1 risk genotypes influence DNA methylation across multiple genomic elements in APOL1-APOL4- MYH9 region in African Americans.Clinical epigenetics · 2026Article
- Apolipoproteins L involvement in immunity.Journal of human immunity · 2026Review
- Three-dimensional interactive network: Mitochondrial-metabolic-calcium homeostasis driving Alzheimer's disease.Genes & diseases · 2026Review
- Bioinformatics and Immunohistochemistry Reveal the Diagnostic and Mechanistic Role of the Cuproptosis-Related Genes SMOC2/THY1 in Liver Fibrosis.Journal of cellular and molecular medicine · 2026Article
- Pomolic acid alleviates CClScientific reports · 2026Article
- Hepatoprotective effects of carvacrol: molecular mechanisms and insights from pre-clinical Studies.Molecular biology reports · 2026Review
- Adh1-Programmed SNF1 Phosphogradients Decrypt Morphogenesis in Candida albicans: Chemical Interrogation Unveils Hyphal Transition Thresholds.Microbial biotechnology · 2026Article
- A small molecule targets LIC1 to suppress lung tumor growth by inducing autophagy.Nature chemical biology · 2026Article
- Discovery of Exoticoumarins A-L: New Anti-Inflammatory Coumarin Derivatives fromInternational journal of molecular sciences · 2026Article
- From calcium pump to metabolic hub: emerging genetic phenotypes and metabolic networks of SERCA2 in skeletal muscle.Frontiers in physiology · 2026Review
- Nanomedicine-Driven Modulation of Signaling Pathways in Hepatic Fibrosis.International journal of nanomedicine · 2026Review
- Rubimaillin ameliorates liver fibrosis by triggering the ferroptosis of activated hepatic stellate cells through targeting CPT1A.International journal of biological sciences · 2026Article
- Immune cell involvement in ulcer repair in radiation esophagitis and its role in the TGF-β1/p38MAPK/FN axis (Review).Molecular and clinical oncology · 2025Review
- Multi-omics and machine learning identify FN1 and ALDH2 as diagnostic biomarkers and therapeutic targets in early and late diabetic kidney disease.Renal failure · 2025Article
- IL33-induced lipid droplet formation in mature low-density neutrophils drives colorectal cancer liver metastasis.Cellular & molecular immunology · 2025Article
- APOL2 Stabilizes Ku80 to Confer NHEJ-Mediated Radioresistance in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- [Research progress on cellular metabolic reprogramming in skin fibrosis].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Review
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Funding
Abstract
Liver fibrosis is an urgent clinical problem without effective therapies. Here we conducted a high-content screening on a natural Euphorbiaceae diterpenoid library to identify a potent anti-liver fibrosis lead, 12-deoxyphorbol 13-palmitate (DP). Leveraging a photo-affinity labeling approach, apolipoprotein L2 (APOL2), an endoplasmic reticulum (ER)-rich protein, was identified as the direct target of DP. Mechanistically, APOL2 is induced in activated hepatic stellate cells upon transforming growth factor-β1 (TGF-β1) stimulation, which then binds to sarcoplasmic/ER calcium ATPase 2 (SERCA2) to trigger ER stress and elevate its downstream protein kinase R-like ER kinase (PERK)-hairy and enhancer of split 1 (HES1) axis, ultimately promoting liver fibrosis. As a result, targeting APOL2 by DP or ablation of APOL2 significantly impairs APOL2-SERCA2-PERK-HES1 signaling and mitigates fibrosis progression. Our findings not only define APOL2 as a novel therapeutic target for liver fibrosis but also highlight DP as a promising lead for treatment of this symptom.
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