ArticleThe Journal of clinical investigation2018
Aortic carboxypeptidase-like protein, a WNT ligand, exacerbates nonalcoholic steatohepatitis.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 54 citations in OpenAlex.
- Aortic carboxypeptidase-like protein potentiates β1 integrin signaling in mesenchymal progenitors.Life science alliance · 2026Article
- Aebp1 loss in osteoprogenitors leads to skeletal defects resembling Ehlers-Danlos Syndrome by diminishing Wnt/β-catenin signaling.JCI insight · 2026Article
- Identification of foam cell like M2 macrophages, AEBP1 biomarkers, and resveratrol as potential therapeutic in MASLD using Ecotyper and WGCNA.Scientific reports · 2025Article
- The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Inactive metallopeptidase homologs: the secret lives of pseudopeptidases.Frontiers in molecular biosciences · 2024Review
- Single-cell transcriptomics analysis of proliferative diabetic retinopathy fibrovascular membranes reveals AEBP1 as fibrogenesis modulator.JCI insight · 2023Article
- ACLP Activates Cancer-Associated Fibroblasts and Inhibits CD8+ T-Cell Infiltration in Oral Squamous Cell Carcinoma.Cancers · 2023Article
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- Case report: Two individuals withFrontiers in genetics · 2023Article
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- CD8Nature communications · 2021Article
- Current Options and Future Directions for NAFLD and NASH Treatment.International journal of molecular sciences · 2021Review
- Exercise in mice ameliorates high-fat diet-induced nonalcoholic fatty liver disease by lowering HMGCS2.Aging · 2021Article
- Aortic carboxypeptidase-like protein regulates vascular adventitial progenitor and fibroblast differentiation through myocardin related transcription factor A.Scientific reports · 2021Article
- Animal Models of Ehlers-Danlos Syndromes: Phenotype, Pathogenesis, and Translational Potential.Frontiers in genetics · 2021Review
- The liver-brain-gut neural arc maintains the TNature · 2020Article
- The Ehlers-Danlos syndromes.Nature reviews. Disease primers · 2020Review
- Mechanisms of aortic carboxypeptidase-like protein secretion and identification of an intracellularly retained variant associated with Ehlers-Danlos syndrome.The Journal of biological chemistry · 2020Article
- Transcriptional Regulation in Non-Alcoholic Fatty Liver Disease.Metabolites · 2020Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Incidence of nonalcoholic steatohepatitis (NASH), which is considered a hepatic manifestation of metabolic syndrome, has been increasing worldwide with the rise in obesity; however, its pathological mechanism is poorly understood. Here, we demonstrate that the hepatic expression of aortic carboxypeptidase-like protein (ACLP), a glycosylated, secreted protein, increases in NASH in humans and mice. Furthermore, we elucidate that ACLP is a ligand, unrelated to WNT proteins, that activates the canonical WNT pathway and exacerbates NASH pathology. In the liver, ACLP is specifically expressed in hepatic stellate cells (HSCs). As fatty liver disease progresses, ACLP expression is enhanced via activation of STAT3 signaling by obesity-related factors in serum. ACLP specifically binds to frizzled-8 and low-density lipoprotein-related receptor 6 to form a ternary complex that activates canonical WNT signaling. Consequently, ACLP activates HSCs by inhibiting PPARγ signals. HSC-specific ACLP deficiency inhibits fibrosis progression in NASH by inhibiting canonical WNT signaling in HSCs. The present study elucidates the role of canonical WNT pathway activation by ACLP in NASH pathology, indicating that NASH can be treated by targeting ACLP-induced canonical WNT pathway activation in HSCs.
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