Hepatic stellate cell activation and pro-fibrogenic signals

  • Chandrashekhar R. Gandhi
    Address: Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, 3333 Burnett Avenue, Cincinnati, OH, USA. Tel.: +1 513 517 1090; fax: +1 513 558 8677.
    Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
    Cincinnati VA Medical Center, Cincinnati, OH, USA
    Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
    Search for articles by this author
Published:September 19, 2017DOI:
      Liver fibrosis is a primary response to injury of etiologies including metabolic abnormalities, viral (hepatitis C and B virus [HCV/HBV]) and other infections, toxins and drugs. Chronic exposure to the injury agent(s) can cause fibrosis to progress to irreversible cirrhosis. Although effective therapies for HCV-induced fibrosis are now available, the new challenge is the alarming increase in liver fibrosis/cirrhosis due to non-alcoholic and alcoholic steatohepatitis. A clear understanding of the mechanisms of hepatic fibrosis/cirrhosis is critical.


      AcCHO (acetaldehyde), ADPN (adiponectin), Akt (protein kinase B), aHSC (activated hepatic stellate cell), Ang1 (angiopoietin-1), Ang II (angiotensin II), AP1 (activator protein-1), AT1R (angiotensin receptor 1), cAMP (cyclic adenosine monophosphate), Bcl2 (B-cell lymphoma 2), bFGF (basic fibroblast growth factor), C/EBP (CCAAT-enhancer-binding protein), CTGF (connective tissue growth factor), ECM (extracellular matrix), EF (endothelial fenestration), EGF (epidermal growth factor), ERK (Extracellular signal-regulated kinase), Ets (erythroblast transformation specific), FXR (farnesoid X receptor), GTP (Guanosine-5′-triphosphate), HSC (hepatic stellate cell), H2O2 (hydrogen peroxide), ICAM1 (intercellular cell adhesion molecule 1), IFN (interferon), IL (interleukin), JAK (janus kinase), KC (Kupffer cell), KLF6 (Kruppel like factor 6), Lhx2 (the LIM homodimer protein), LepR (leptin receptor (CD295, OB-R)), LPS (Gram-negative bacterial lipopolysaccharide), MAPK (mitogen-activated protein kinase), MMP (matrix metalloproteinase), (macrophage), N (neutrophil), NADP (nicotinamide adenine dinucleotide phosphate), NFκB (nuclear factor kappa-light-chain enhancer of activated B cells), NOX (NADPH oxidase), OPN (osteopontin), PDGF (platelet-derived growth factor), PI3K (phosphatidylinositol-3-kinase), PK (protein kinase), PPAR (peroxisome proliferator-activated receptor), RAR (retinoid acid receptor), ROS (reactive oxygen species), RXR (retinoid X receptor), SEC (sinusoidal endothelial cell), SHP (small heterodimer partner), SMA (smooth muscle actin), Smad (small mother against decapentaplegic), Sp1 (specificity protein 1), STAT (signal transducer and activator of transcription), TGF (transforming growth factor), TIMP (tissue inhibitor of metalloproteinase), TLR (toll-like receptor), TNF (tumor necrosis factor), uPa (urokinase-type plasminogen activator), VEGF (vascular endothelial growth factor)


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Hepatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Mederacke I.
        • Hsu C.C.
        • Troeger J.S.
        • Huebener P.
        • Mu X.
        • Dapito D.H.
        • et al.
        Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology.
        Nat Commun. 2013; 4: 2823
        • Kayama Y.
        • Wang P.
        • Brenner D.A.
        • Kisseleva T.
        Gandhi C.R. Pinzani M. Stellate cells in health and disease. Elsevier Press, 2015: 87-106
        • Puche J.E.
        • Saiman Y.
        • Friedman S.L.
        Hepatic stellate cells and liver fibrosis.
        Compr Physiol. 2013; 3: 1473-1492
        • Campana L.
        • Iredale J.
        Matrix metalloproteinases and their inhibitors.
        in: Gandhi C.R. Pinzani M. Stellate cells in health and disease. Elsevier Press, 2015: 107-124
        • Fabre T.
        • Kared H.
        • Friedman S.L.
        • Shoukry N.H.
        IL-17A enhances the expression of profibrotic genes through upregulation of the TGF-β receptor on hepatic stellate cells in a JNK-dependent manner.
        J Immunol. 2014; 193: 3925-3933
        • Mann J.
        • Mann D.A.
        Transcriptional regulation of hepatic stellate cells.
        Adv Drug Delivery Rev. 2009; 61: 497-512
        • Marra F.
        • Caligiuri A.
        Cytokine production and signaling in stellate cells.
        in: Gandhi C.R. Pinzani M. Stellate cells in health and disease. Elsevier Press, 2015: 63-86
        • Granzow M.
        • Schierwagen R.
        • Klein S.
        • Kowallick B.
        • Huss S.
        • Linhart M.
        • et al.
        Angiotensin-II type 1 receptor-mediated Janus kinase 2 activation induces liver fibrosis.
        Hepatology. 2014; 60: 334-348
        • Seki E.
        • De Minicis S.
        • Osterreicher C.H.
        • Kluwe J.
        • Osawa Y.
        • Brenner D.A.
        • et al.
        TLR4 enhances TGF-beta signaling and hepatic fibrosis.
        Nat Med. 2007; 13: 1324-1332
        • Harvey S.A.K.
        • Dangi A.
        • Tandon A.
        • Gandhi C.R.
        The transcriptomic response of rat hepatic stellate cells to endotoxin: Implications for hepatic inflammation and immune regulation.
        PLoS One. 2013; 8: e82159

      CHORUS Manuscript

      View Open Manuscript