ArticleExperimental & molecular medicine2021
Splenectomy improves liver fibrosis via tumor necrosis factor superfamily 14 (LIGHT) through the JNK/TGF-β1 signaling pathway.
Article in Experimental & molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 39 citations in OpenAlex.
- Comment on "Validation of Baveno VII criteria for recompensation in patients with decompensated cirrhosis treated by laparoscopic splenectomy and azygoportal disconnection".Journal of gastroenterology · 2026Article
- Acute-on-Chronic Liver Failure: An Eroded Cliff Hit by a Storm-A Narrative Review.International journal of molecular sciences · 2026Review
- Tanshinone IIA Attenuates Pulmonary Fibrosis via Dual Inhibition of JNK and Smad Signaling.Antioxidants (Basel, Switzerland) · 2026Article
- Tumor Necrosis Factor Superfamily 14: A Potential Predictor of Atrial Fibrillation Recurrence After Catheter Ablation.Clinical cardiology · 2026Article
- Rare Causes of Portal Vein Thrombosis and Occlusion: A Narrative Review.Diagnostics (Basel, Switzerland) · 2026Review
- Validation of Baveno VII criteria for recompensation in patients with decompensated cirrhosis treated by laparoscopic splenectomy and azygoportal disconnection.Journal of gastroenterology · 2026Article
- TNF superfamily member 14 drives post-influenza depletion of alveolar macrophages, enabling secondary pneumococcal pneumonia.The Journal of clinical investigation · 2026Article
- Lactylation in liver fibrosis: from molecular mechanisms to targeted therapeutic strategies.Frontiers in pharmacology · 2026Review
- Congenital hepatic fibrosis and related ciliopathies across the life course: current management, disease burden, and unmet needs in the era of genomic diagnosis and translational therapeutics.Frontiers in pediatrics · 2026Review
- Article
- Genetic ablation of interleukin-17A augments fibrosis in a mouse model of cholestatic liver injury.PloS one · 2026Article
- Splenectomy reduces shear stress and inflammation in liver endothelial cells during regeneration after partial hepatectomy in mice.Scientific reports · 2025Article
- Identification of novel therapeutic targets for liver fibrosis, cirrhosis, and hepatocellular carcinomaClinical and experimental hepatology · 2025Article
- Review
- Splenectomy and risk of hepatocellular carcinoma.World journal of hepatology · 2025Review
- Spleen volume after stage-I associated liver partition and portal vein ligation for staged hepatectomy predicts future liver remnant.Langenbeck's archives of surgery · 2025Article
- A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.Genome biology · 2025Article
- Article
- TNFSF14 (LIGHT) in intestinal inflammation: balancing immune activation and resolution in IBD.Frontiers in immunology · 2025Review
- A Turbo-Charging System-Like Contrast Agent for MRI-Guided STING Pathway-Activated Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Splenectomy has been reported to improve liver fibrosis in patients with cirrhosis and hypersplenism. However, the mechanisms remain unclear. Tumor necrosis factor superfamily 14 (TNFSF14; also known as LIGHT) is highly expressed in the context of fibrosis and promotes disease progression in patients with fibrotic diseases such as pulmonary and skin fibrosis. Here, we determined whether splenectomy controls the production of LIGHT to improve liver fibrosis. Splenectomy reduced serum LIGHT levels in cirrhotic patients with hypersplenism and a ConA-induced liver fibrosis mouse model. Blocking LIGHT resulted in the downregulation of TGF-β1 in RAW264.7 cells. LIGHT treatment of RAW264.7 and JS1 cells in coculture regulated transforming growth factor-β1 (TGF-β1) expression through the activation of JNK signaling. Small interfering RNA-mediated silencing of lymphotoxin β receptor (LTβR) in macrophages resulted in pronounced decreases in the levels of fibrosis and αSMA in JS1 cells. These results indicated that LIGHT bound to LTβR and drove liver fibrosis in vitro. Blocking TGF-β1 abolished the effect of LIGHT in vitro. Furthermore, the administration of recombinant murine LIGHT protein-induced liver fibrosis with splenectomy, while blocking LIGHT without splenectomy improved liver fibrosis in vivo, revealing that the decrease in fibrosis following splenectomy was directly related to reduced levels of LIGHT. Thus, high levels of LIGHT derived from the spleen and hepatic macrophages activate JNK signaling and lead to increased TGF-β1 production in hepatic macrophages. Splenectomy attenuates liver fibrosis by decreasing the expression of LIGHT.
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