ArticleThe Journal of clinical investigation2021
Sparcl1 promotes nonalcoholic steatohepatitis progression in mice through upregulation of CCL2.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 79 citations in OpenAlex.
- The versatile interplay between steatotic liver disease and liver cancer.Nature reviews. Cancer · 2026Review
- The secreted protein SPARCL1 suppresses tumor progression in papillary thyroid carcinoma via SLC3A2-mediated ferroptosis.Endocrine-related cancer · 2026Article
- Chemokines and chemokine receptors in metabolic dysfunction-associated steatohepatitis: pathogenic mechanisms and clinical implications.Cellular & molecular biology letters · 2026Review
- Advances in Adipose Tissue Biology.Endocrine reviews · 2026Review
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Trends and factors associated with liver fibrosis-cirrhosis complicated with pneumonia-influenza mortality in U.S. Counties: a CDC WONDER and CHR database analysis.Frontiers in public health · 2026Article
- Integrated bioinformatics decoding of the MASLD ceRNA network reveals novel therapeutic targets.Clinical and experimental medicine · 2025Article
- Role of the E26 transformation specific transcription factor family in metabolic disorders.Journal of endocrinological investigation · 2025Review
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Identification of CTSK as a TLR-related critical biomarker in liver cirrhosis via integrative bioinformatics and pathological characterization.Scientific reports · 2025Article
- Establishment and characterization of preclinical model of primary ovarian squamous cell carcinoma.Human cell · 2025Article
- Toward Proteomic Precision Medicine for Steatotic Liver Diseases.Journal of the American Heart Association · 2025Article
- The lung microvasculature promotes alveolar type 2 cell differentiation via secreted SPARCL1.Stem cell reports · 2025Article
- Isoschaftoside in Fig Leaf Tea Alleviates Nonalcoholic Fatty Liver Disease in Mice via the Regulation of Macrophage Polarity.Nutrients · 2025Article
- Immune Microenvironment on the Molecular Mechanisms and Therapeutic Targets of MAFLD.ImmunoTargets and therapy · 2025Review
- The oncogenic functions of SPARCL1 in bladder cancer.Journal of cellular and molecular medicine · 2024Article
- Mulberry andFood science & nutrition · 2024Article
- Vascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation.Nature communications · 2024Article
- CAR-T Cell Therapy: Advances in Kidney-Related Diseases.Kidney diseases (Basel, Switzerland) · 2024Review
- A genetic mouse model of lean-NAFLD unveils sexual dimorphism in the liver-heart axis.Communications biology · 2024Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of chronic liver disease ranging from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH). However, the molecular mechanisms of NASH progression remain incompletely understood. White adipose tissue (WAT) has emerged as an important endocrine organ and contributes not only to the initial stage of NAFLD, but also to its severity. In the current study, through transcriptomic analysis we identified increased expression of Sparcl1, a secreted glycoprotein, in the WAT from NASH mice. Plasma Sparcl1 levels were similarly elevated and positively correlated with hepatic pathological features in NASH patients. Functional studies showed that both chronic injection of recombinant Sparcl1 protein and overexpression of Sparcl1 exaggerated hepatic inflammation and liver injury in mice. In contrast, genetic ablation of Sparcl1, knockdown of Sparcl1 in WAT, and treatment with a Sparcl1-neutralizing antibody dramatically alleviated diet-induced NASH pathogenesis. Mechanistically, Sparcl1 promoted the expression of C-C motif chemokine ligand 2 (CCL2) in hepatocytes through binding to Toll-like receptor 4 (TLR4) and activation of the NF-κB/p65 signaling pathway. Genetically or pharmacologically blocking the CCL2/CCR2 pathway attenuated the hepatic inflammatory response evoked by Sparcl1. Thus, our results demonstrated an important role for Sparcl1 in NASH progression, suggesting a potential target for therapeutic intervention.
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