ArticleGut2017
Selective targeting of lysyl oxidase-like 2 (LOXL2) suppresses hepatic fibrosis progression and accelerates its reversal.
Article in Gut, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers, 1 of them a synthesis that pooled it.
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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
164 citing papers in PubMed, 1 synthesis or guideline pooled it, 292 citations in OpenAlex.
- Non-invasive biomarkers prognostic of decompensation events in NASH cirrhosis: a systematic literature review.Journal of molecular medicine (Berlin, Germany) · 2024Pooled it
- Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis.Hepatology communications · 2024Trial
- Zirconium-89 Labeling and Preliminary Evaluation of Simtuzumab as a Candidate Positron Emission Tomography (PET) Imaging Agent for Human Lysyl Oxidase-like 2 (LOXL2) in the Extracellular Matrix of Solid Tumors.ACS pharmacology & translational science · 2026Article
- Lysyl oxidase (LOX) family proteins in extracellular matrix homeostasis: roles in disease and radiation-induced pathogenesis.Molecular biology reports · 2026Review
- The instructive scar - the dynamic role of extracellular matrix in biliary pathophysiology.Disease models & mechanisms · 2026Review
- Drug Development for MASH-Related Compensated Cirrhosis: Past, Present and Future.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- The inflammatory/fibrotic axis across organs: myelofibrosis as a model of reversibility.JCI insight · 2026Review
- Expression of Lysyl Oxidase-Related Protein and Effect of Lysyl Oxidase Inhibition in Cyclosporine-Induced Nephropathy Mouse Model.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The Matrix Reloaded: The Hepatic Matrisome as a Therapeutic Opportunity to Fight Liver Fibrosis.Biomolecules · 2026Review
- The mechano-immunological landscape in the tumor microenvironment: From mechanical sensing to a new therapeutic paradigm.Materials today. Bio · 2026Review
- Cell type-resolved analysis identifies LOXL2⁺ fibroblasts as key drivers of malignant stromal remodeling in hepatocellular carcinoma.Discover oncology · 2026Article
- Mechanisms and reversal strategies of liver fibrosis: from regulation of cell fate to clinical translation.Journal of translational medicine · 2026Review
- Fibrotic microRNAs in the suppression of HSC activation and ECM deposition to facilitate the regression of hepatic fibrosis in zebrafish.Journal of molecular medicine (Berlin, Germany) · 2026Article
- The Extracellular Matrix in Liver Regeneration: Biological and Therapeutic Insights.Bioengineering (Basel, Switzerland) · 2026Review
- Targeting Tumor-Associated Macrophages to Reshape the Immuno-Mechanical Landscape: Molecular Mechanisms and Therapeutic Strategies.International journal of biological sciences · 2026Review
- Beyond Organ-Specific Therapies: A Unified Approach to Multi-Organ Fibrosis.Drug design, development and therapy · 2026Review
- Distinct collagen resolution dynamics in early versus advanced liver fibrosis: a quantitative SHG/TPEF study in mice.International journal of clinical and experimental pathology · 2026Article
- Is there a link between fascia and cancer? From potential mechanisms to future treatment options.Frontiers in physiology · 2026Review
- A novel cell-permeable LOXL2 inhibitor PAT-1251 potently suppresses biliary liver fibrosis via collagen crosslinking-dependent and -independent mechanisms.Hepatology communications · 2026Article
- Hepatic stellate cells in liver fibrosis: From biology to pathology.Open veterinary journal · 2025Review
104 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND/
aimsWe studied the role of lysyl oxidase-like 2 (LOXL2) in collagen crosslinking and hepatic progenitor cell (HPC) differentiation, and the therapeutic efficacy of a LOXL2-blocking monoclonal antibody on liver fibrosis progression/reversal in mice.
methodsAnti-LOXL2 antibody, control antilysyl oxidase antibody or placebo was administered during thioacetamide (TAA)-induced fibrosis progression or during recovery. Therapeutic efficacy in biliary fibrosis was tested in BALB/c.
resultsLOXL2 was virtually absent from healthy but strongly induced in fibrotic liver, with predominant localisation within fibrotic septa. Delayed anti-LOXL2 treatment of active TAA fibrosis significantly reduced collagen crosslinking and histological signs of bridging fibrosis, with a 53% reduction in morphometric collagen deposition. In established TAA fibrosis, LOXL2 inhibition promoted fibrosis reversal, with enhanced splitting and thinning of fibrotic septa, and a 45% decrease in collagen area at 4 weeks of recovery. In the Mdr2-/- and DDC-induced models of biliary fibrosis, anti-LOXL2 antibody similarly achieved significant antifibrotic efficacy and suppressed the ductular reaction, while hepatocyte replication increased. Blocking LOXL2 had a profound direct effect on primary EpCAM(+) HPC behaviour in vitro, promoting their differentiation towards hepatocytes, while inhibiting ductal cell lineage commitment.
conclusionsLOXL2 mediates collagen crosslinking and fibrotic matrix stabilisation during liver fibrosis, and independently promotes fibrogenic HPC differentiation. By blocking these two convergent profibrotic pathways, therapeutic LOXL2 inhibition attenuates both parenchymal and biliary fibrosis and promotes fibrosis reversal.
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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.