From: Evolving concepts of liver fibrogenesis provide new diagnostic and therapeutic options
Parameter | Pathobiochemical basis | Potential serum markers of fibrosis | Therapeutic approach |
---|---|---|---|
TGF-β | Fibrogenic master cytokine, up-regulation in fibrotic liver; inducer of epithelial-mesenchymal transition (EMT) | Elevation by up-regulation in the fibrotic liver, release from necrotic hepatocytes and reduced hepatic clearance | Inhibition of TGF-β, blockade of intracellular signalling |
BMP-7 | TGF-β antagonist: anti-apoptotic; anti-inflammatory; anti-EMT | Elevation in serum, indicator of slow fibrosis? | BMP-7 or BMP-7 peptide fragments antagonize TGF-β, antifibrotic effect, stimulation of liver regeneration |
TGF-β/BMP-7 Ratio | Determines epithelial-mesenchymal transition (EMT) and profibrogenic action of TGF-β | Potentially of prognostic significance for estimation of the progression rate of fibrosis (rapid versus slow fibrosis) | Modulation of the ratio by addition of recombinant BMP-7 has an antifibrotic effect |
CTGF | Down-stream modulator protein of TGF-β, influences functional TGF-β/BMP-7 ratio by elevation of TGF-β and decrease of BMP-7 action | Elevation under conditions of active fibrogenesis, decrease with advancing cirrhosis and in the terminal stage without fibrogenic activity | Inhibition of CTGF expression by siRNAs or blocking with humanized monoclonal anti-CTGF antibodies (FG-3019, FibroGen); has a strong antifibrotic effect |
Fibrocytes | Bone marrow-derived progenitor cells of fibroblasts increase the pool of fibroblasts in the fibrotic liver | Flow-cytometric detection of CD34+, CD45+, and collagen-1+ cells in peripheral blood or buffy coat leucocytes; potential indicator of increased influx into the damaged liver tissue | Hormonal modulation of release of fibrocytes from bone marrow and integration into the liver? |
G-CSF | Recruitment of bone marrow-derived cells in the circulation and stimulation of their homing in the fibrotic liver tissue | Elevated concentrations, relation to fibrogenesis not yet established | G-CSF triggered haematopoietic stem cells or G-CSF itself accelerates healing of experimental liver damage and improves the survival rate |