ArticleWorld journal of gastroenterology2015
Early activated hepatic stellate cell-derived molecules reverse acute hepatic injury.
Article in World journal of gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- The Impact of Liver Steatosis on Interleukin and Growth Factors Kinetics during Chronic Hepatitis C Treatment.Journal of clinical medicine · 2024Article
- Fibroblasts in liver cancer: functions and therapeutic translation.The lancet. Gastroenterology & hepatology · 2023Review
- Divergent effect of Birinapant, and BV6 SMAC mimetic on TNFα induced NF-κB signaling and cell viability in activated hepatic stellate cells.Molecular biology reports · 2023Article
- The Effect of Treatment-Induced Viral Eradication on Cytokine and Growth Factor Expression in Chronic Hepatitis C.Viruses · 2022Article
- Autophagy and Exosomes: Cross-Regulated Pathways Playing Major Roles in Hepatic Stellate Cells Activation and Liver Fibrosis.Frontiers in physiology · 2021Review
- RNA sequencing reveals changes in the microRNAome of transdifferentiating hepatic stellate cells that are conserved between human and rat.Scientific reports · 2020Article
- Curcumin Recovers Intracellular Lipid Droplet Formation Through Increasing Perilipin 5 Gene Expression in Activated Hepatic Stellate Cells In Vitro.Current medical science · 2019Article
- Role of Natural Phenolics in Hepatoprotection: A Mechanistic Review and Analysis of Regulatory Network of Associated Genes.Frontiers in pharmacology · 2019Review
- The Effects of Conditioned Medium Derived from Mesenchymal Stem Cells Cocultured with Hepatocytes on Damaged Hepatocytes and Acute Liver Failure in Rats.Stem cells international · 2018Article
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
aimTo test whether hepatic stellate cells (HSCs) at different activation stages play different roles in acetaminophen (APAP)-induced acute liver injury (ALI).
methodsHSCs were isolated from mouse liver and cultured in vitro. Morphological changes of initiation HSCs [HSCs (5d)] and perpetuation HSCs [HSCs (p3)] were observed by immunofluorescence and transmission electron microscopy. The protective effects of HSC-derived molecules, cell lysates and HSC-conditioned medium (HSC-CM) were tested in vivo by survival and histopathological analyses. Liver injury was determined by measuring aminotransferase levels in the serum and by histologic examination of tissue sections under a light microscope. Additionally, to determine the molecular mediators of the observed protective effects of initiation HSCs, we examined HSC-CM using a high-density protein array.
resultsHSCs (5d) and HSCs (p3) had different morphological and phenotypic traits. HSCs (5d) presented a star-shaped appearance with expressing α-SMA at non-uniform levels between cells. However, HSCs (p3) evolved into myofibroblast-like cells without lipid droplets and expressed a uniform and higher level of α-SMA. HSC-CM (5d), but not HSC-CM (p3), provided a significant survival benefit and showed a dramatic reduction of hepatocellular necrosis and panlobular leukocyte infiltrates in mice exposed to APAP. However, this protective effect was abrogated at higher cell masses, indicating a therapeutic window of effectiveness. Furthermore, the protein array screen revealed that HSC-CM (5d) was composed of many chemokines and growth factors that correlated with inflammatory inhibition and therapeutic activity. When compared with HSC-CM (p3), higher levels of monocyte chemoattractant protein-1, macrophage inflammatory protein-1γ, hepatocyte growth factor, interleukin-10, and matrix metalloproteinase-2, but lower levels of stem cell factor and Fas-Ligand were observed in HSC-CM (5d).
conclusionThese data indicated that initiation HSCs and perpetuation HSCs were different in morphology and protein expression, and provided the first experimental evidence of the potential medical value of initiation HSC-derived molecules in the treatment of ALI.
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