ArticlePloS one2013
Hypoxia-inducible factor-1alpha and MAPK co-regulate activation of hepatic stellate cells upon hypoxia stimulation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- Hypoxia in MASLD: a spatial determinant of the pathogenesis.Trends in molecular medicine · 2026Review
- Therapeutic Targets for Hepatic Fibrosis Driven by Hypoxia-Mediated Hepatic Stellate Cell Activation.Biomolecules · 2026Review
- Skeletal Muscle miRNA Patterns in High-Altitude Trekkers: Exploratory Identification of Molecular Signatures of Cellular and Endocrine Adaptation.Biomolecules · 2026Article
- A Review of HIF-1α-Mediated Integration of Metabolic Reprogramming, Mitochondrial Function, and PI3K/Akt-MAPK-Nrf2-NF-κB Signaling.Antioxidants (Basel, Switzerland) · 2026Review
- Vitamin D and hypoxia-inducible factors signaling interplay: A hypothesis-driven review of therapeutic strategies for acute cerebral infarction.Metabolic brain disease · 2026Review
- The effects of the "living high-training low" model on key proteins involved in cellular aerobic and anaerobic metabolism in male C57BL/6J mice.Physiological reports · 2026Article
- Integrated Machine Learning and Multi-Omics Analysis Identifies Mitophagy-Related Core Genes and Mechanisms in Non-Alcoholic Fatty Liver Disease.Journal of inflammation research · 2026Article
- Interactions between the metabolic reprogramming of liver cancer and tumor microenvironment.Frontiers in immunology · 2025Review
- Regulation of CMGC kinases by hypoxia.BMB reports · 2023Review
- Unraveling the Emerging Niche Role of Hepatic Stellate Cell-derived Exosomes in Liver Diseases.Journal of clinical and translational hepatology · 2023Review
- Research progress of traditional Chinese medicine in improving hepatic fibrosis based on inhibiting pathological angiogenesis.Frontiers in pharmacology · 2023Review
- Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis.Open life sciences · 2023Article
- The evolving role of long noncoding RNA HIF1A-AS2 in diabetic retinopathy: a cross-link axis between hypoxia, oxidative stress and angiogenesis via MAPK/VEGF-dependent pathway.Redox report : communications in free radical research · 2022Article
- Effect of Curcumin on Attenuation of Liver Cirrhosis via Genes/Proteins and Pathways: A System Pharmacology Study.Nutrients · 2022Article
- Evaluation of the Mechanism of Jiedu Huazhuo Quyu Formula in Treating Wilson's Disease-Associated Liver Fibrosis by Network Pharmacology Analysis and Molecular Dynamics Simulation.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Profiles of messenger RNAs and MicroRNAs in hypoxia-induced hepatic stellate cells.Annals of translational medicine · 2021Article
- Review
- The roles and mechanisms of hypoxia in liver fibrosis.Journal of translational medicine · 2021Review
- Curcumin relieves the arecoline-induced fibrosis of oral mucosal fibroblasts via inhibiting HIF-1α/TGF-β/CTGF signaling pathway: anToxicology research · 2021Article
- The Power of Plasticity-Metabolic Regulation of Hepatic Stellate Cells.Cell metabolism · 2021Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatic stellate cell (HSC) plays a key role in pathogenesis of liver fibrosis. During liver injury, hypoxia in local micro-environment is inevitable. Hif-1α is the key transcriptional regulation factor that induces cell's adaptive responses to hypoxia. Recently, it was reported that MAPK is involved in regulation of Hif-1α activity.
aimsTo explore whether Hif-1α regulates HSC activation upon hypoxia, and whether MAPK affects Hif-1α-regulated signaling cascades, thus providing new targets for preventing liver fibrosis.
methodsHif-1α expression in livers of Schistosomajaponicum infected BALB/c mice was detected with western blot and immunohistochemistry. A rat cell line of HSC, HSC-T6, was cultured in 1% oxygen. HSC activation, including F-actin reorganization, increase of vimentin and α-SMA, was detected with western blot or immunocytochemistry. Cells were transfected with specific siRNA to Hif-1α, expression of activation markers, transcription of fibrosis-promoting cytokines, secretion of collagen I were detected with western blot, Real Time PCR and ELISA. Lysate from HSC-T6 cells pretreated with PD98059, a specific MEK1 pharmacological inhibitor, was subjected to detect Hif-1α ubiquitination and nuclear translocation with western blot and immunoprecipitation. RESULTS AND
conclusionsHif-1α apparently increased in liver tissues of Schistosomajaponicum infected mice. 1% O2 induced F-actin reorganization, increase of Hif-1α, vimentin and α-SMA in HSC-T6 cells. Hif-1α Knockdown inhibited HSC-T6 activation, transcription of IL-6, TGF-β and CTGF and secretion of collagen I from HSC-T6 cells upon hypoxia. Inhibition of MAPK phosphorylation enhanced Hif-1α ubiquitination, and inhibited Hif-1α translocation into nucleus. Conclusively, Hif-1α and MAPK participate in HSC activation upon hypoxia.
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