ArticleInternational journal of molecular sciences2018
Niemann-Pick Type C2 Protein Regulates Free Cholesterol Accumulation and Influences Hepatic Stellate Cell Proliferation and Mitochondrial Respiration Function.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 26 citations in OpenAlex.
- Urine Proteomics as a Source of Biological Information and Outcome Predictor in Living Kidney Transplantation.Molecular & cellular proteomics : MCP · 2026Article
- NPC2 suppresses osteolytic metastasis in lung adenocarcinoma via the AKT/mTOR pathway and tumor-osteoclast crosstalk.iScience · 2026Article
- Starve-Feed Cycles Direct Quiescence to Proliferation Transitions inbioRxiv : the preprint server for biology · 2026Article
- ALKBH5-mediated NPC2 mRNA mFunctional & integrative genomics · 2025Article
- Metabolic Sparks in the Liver: Metabolic and Epigenetic Reprogramming in Hepatic Stellate Cells Activation and Its Implications for Human Metabolic Diseases.Diabetes & metabolism journal · 2025Review
- Prognostic significance of high NPC2 expression in gastric cancer.Scientific reports · 2023Article
- Niemann-Pick Disease Type C (NPDC) by Mutation ofAntioxidants (Basel, Switzerland) · 2023Review
- New Perspectives on Cholesterol and Lipoprotein Metabolism.International journal of molecular sciences · 2023Article
- Secretory NPC2 Protein-Mediated Free Cholesterol Levels Were Correlated with the Sorafenib Response in Hepatocellular Carcinoma.International journal of molecular sciences · 2021Article
- Resveratrol Inhibits Hepatic Stellate Cell Activation via the Hippo Pathway.Mediators of inflammation · 2021Article
- RNASeq Analysis ofViruses · 2019Article
- Is autophagy an elective strategy to protect neurons from dysregulated cholesterol metabolism?Neural regeneration research · 2019Review
- Role of Metabolism in Hepatic Stellate Cell Activation and Fibrogenesis.Frontiers in cell and developmental biology · 2018Article
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Authors and funding
6 authors at 3 institutions in 1 country.
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Abstract
Liver fibrosis is the first step toward the progression to cirrhosis, portal hypertension, and hepatocellular carcinoma. A high-cholesterol diet is associated with liver fibrosis via the accumulation of free cholesterol in hepatic stellate cells (HSCs). Niemann-Pick type C2 (NPC2) plays an important role in the regulation of intracellular free cholesterol homeostasis via direct binding with free cholesterol. Previously, we reported that NPC2 was downregulated in liver cirrhosis tissues. Loss of NPC2 enhanced the accumulation of free cholesterol in HSCs and made them more susceptible to transforming growth factor (TGF)-β1. In this study, we showed that knockdown of NPC2 resulted in marked increases in platelet-derived growth factor BB (PDGF-BB)-induced HSC proliferation through enhanced extracellular signal-regulated kinases (ERK), p38, c-Jun N-terminal kinases (JNK), and protein kinase B (AKT) phosphorylation. In contrast, NPC2 overexpression decreased PDGF-BB-induced cell proliferation by inhibiting p38, JNK, and AKT phosphorylation. Although NPC2 expression did not affect caspase-related apoptosis, the autophagy marker light chain 3β (LC3B) was decreased in NPC2 knockdown, and free cholesterol accumulated in the HSCs. The mitochondrial respiration functions (such as oxygen consumption rate, ATP production, and maximal respiratory capacity) were decreased in NPC2 knockdown, and free cholesterol accumulated in the HSCs, while NPC2-overexpressed cells remained normal. In addition, NPC2 expression did not affect the susceptibility of HSCs to lipopolysaccharides (LPS), and U18666A treatment induced free cholesterol accumulation, which enhanced LPS-induced Toll-like receptor 4 (TLR4), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 phosphorylation, interleukin (IL)-1 and IL-6 expression. Our study demonstrated that NPC2-mediated free cholesterol homeostasis controls HSC proliferation and mitochondrial function.
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