ArticleHepatology (Baltimore, Md.)2012
Osteopontin is a novel downstream target of SOX9 with diagnostic implications for progression of liver fibrosis in humans.
Article in Hepatology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 99 citations in OpenAlex.
- A practical toolbox for modelling fibrosis in vitro.Nature biomedical engineering · 2026Review
- BRUCE liver-KO enhances MASLD/MASH development in the steatotic PTEN-KO background by impairing mitochondrial metabolism and activating STAT3.Cell death & disease · 2025Article
- SOX9 plays an essential role in myofibroblast driven hepatic granuloma integrity and parenchymal repair during schistosomiasis-induced liver damage.PLoS pathogens · 2025Article
- Spatial gene regulatory networks driving cell state transitions during human liver disease.EMBO molecular medicine · 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
- Noninvasive identification of SOX9 status using radiomics signatures may help construct personalized treatment strategy in hepatocellular carcinoma.Abdominal radiology (New York) · 2024Article
- Generation of human iPSC-derived 3D bile duct within liver organoid by incorporating human iPSC-derived blood vessel.Nature communications · 2024Article
- Diverse functions of SOX9 in liver development and homeostasis and hepatobiliary diseases.Genes & diseases · 2024Review
- Metabolic inflexibility promotes mitochondrial health during liver regeneration.Science (New York, N.Y.) · 2024Article
- SOX9 Induces Orbital Fibroblast Activation in Thyroid Eye Disease Via MAPK/ERK1/2 Pathway.Investigative ophthalmology & visual science · 2024Article
- Cathepsin D elevates the fibrocalcific activity in human aortic valve cells through the ERK1/2-Sox9 pathway.Frontiers in cardiovascular medicine · 2024Article
- Type IV Collagen and SOX9 Are Molecular Targets of BET Inhibition in Experimental Glomerulosclerosis.International journal of molecular sciences · 2022Article
- Sox9 Expression in the Second Heart Field; A Morphological Assessment of the Importance to Cardiac Development with Emphasis on Atrioventricular Septation.Journal of cardiovascular development and disease · 2022Article
- MicroRNA-15a inhibits hepatic stellate cell activation and proliferation via targeting SRY-box transcription factor 9.Bioengineered · 2022Article
- Pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis.World journal of clinical cases · 2022Review
- Advance of SOX Transcription Factors in Hepatocellular Carcinoma: From Role, Tumor Immune Relevance to Targeted Therapy.Cancers · 2022Review
- Osteopontin as a Regulator of Colorectal Cancer Progression and Its Clinical Applications.Cancers · 2021Review
- Transitional cell carcinoma matrix stiffness regulates the osteopontin and YAP expression in recurrent patients.Molecular biology reports · 2021Article
- Single-cell RNA sequencing reveals spatiotemporal heterogeneity and malignant progression in pancreatic neuroendocrine tumor.International journal of biological sciences · 2021Article
- Tubulointerstitial nephritis antigen-like 1 deficiency alleviates age-dependent depressed ovulation associated with ovarian collagen deposition in mice.Reproductive medicine and biology · 2020Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 4 countries.
Funding
Abstract
unlabelledOsteopontin (OPN) is an important component of the extracellular matrix (ECM), which promotes liver fibrosis and has been described as a biomarker for its severity. Previously, we have demonstrated that Sex-determining region Y-box 9 (SOX9) is ectopically expressed during activation of hepatic stellate cells (HSC) when it is responsible for the production of type 1 collagen, which causes scar formation in liver fibrosis. Here, we demonstrate that SOX9 regulates OPN. During normal development and in the mature liver, SOX9 and OPN are coexpressed in the biliary duct. In rodent and human models of fibrosis, both proteins were increased and colocalized to fibrotic regions in vivo and in culture-activated HSCs. SOX9 bound a conserved upstream region of the OPN gene, and abrogation of Sox9 in HSCs significantly decreased OPN production. Hedgehog (Hh) signaling has previously been shown to regulate OPN expression directly by glioblastoma (GLI) 1. Our data indicate that in models of liver fibrosis, Hh signaling more likely acts through SOX9 to modulate OPN. In contrast to Gli2 and Gli3, Gli1 is sparse in HSCs and is not increased upon activation. Furthermore, reduction of GLI2, but not GLI3, decreased the expression of both SOX9 and OPN, whereas overexpressing SOX9 or constitutively active GLI2 could rescue the antagonistic effects of cyclopamine on OPN expression.
conclusionThese data reinforce SOX9, downstream of Hh signaling, as a core factor mediating the expression of ECM components involved in liver fibrosis. Understanding the role and regulation of SOX9 during liver fibrosis will provide insight into its potential modulation as an antifibrotic therapy or as a means of identifying potential ECM targets, similar to OPN, as biomarkers of fibrosis.
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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.