Keeping with the antifibrotic function of miR-29, miR-29 is reduced in liver biopsies after liver intoxication in mice and after chronic liver disease in humans. The reduced levels of miR- 29 during fibrosis are associated with an increase of extracellular miR-29 in serum depending on the fibrotic stage. Furthermore, our in vitro and in vivo studies on HSC or on BDO-treated fibrotic livers, respectively, suggest that the loss of miR-29 in HSC after TGF-b exposure and during liver fibrogenesis leads to the abolishment of collagen type I and IV repression. Conversely, upregulation of miR-29 levels was observed after stimulation of HSC with the antifibrotic mediator HGF, previously shown to inhibit expression of various collagens. Interestingly, our findings proved that upregulation of miR-29a efficiently can overcome the profibrogenic influence of TGF-b on collagen synthesis. Thus, our findings convincingly demonstrate that HGF mediates antifibrotic signals by influencing miR-29 expression and thereby counteracting the profibrotic activity of TGF-b. During myofibroblastic transition of primary HSC in culture and in the HSCT6 cells after HGF and TGF-b treatment. SMA expression was shown by immunochemistry using the monoclonal FITClabeled 1A4 SMA antibody or by real-time PCR. Thus, enhancing the duration of serum EPO could substantially increase the dosing interval, potentially providing an important therapeutic benefit. Two different strategies-hyperglycosylation and polyethylene glycol-conjugation-have been developed to extend the serum half-life of EPO. One wellestablished modified EPO, darbepoetin alfa, is a heavily glycosylated EPO analogue that has been used for 10 years to treat anemia. Unlike native EPO, which contains one O-linked and three N-linked carbohydrate chains with a maximum of 14 sialic acids, darbepoetin alfa was engineered to include two additional N-linked carbohydrate chains containing a maximum of 22 sialic acids. Micera, another recently introduced and commercially available modified EPO, is a pegylated form made by linking the N-terminal amino lysine group of epoetin beta with methoxy polyethylene glycol-succinimidyl butanoic acid through amide bonds. Consistent with a previous report, the in vitro bioactivity of darbepoetin alfa was lower than r-EPO due to its high sialic acid content.