The increased MMP-2/TIMP-2 and suppressed MMP-9/TIMP-1 ratios in IHC and in real-time polymerase chain reaction (RT-PCR) seemed to correlate with the degree of liver fibrosis.
Outcome variables were: a) liver fibrosis (Metavir score) [fibrosis stage (F0, F1, F2, F3 and F4) and advanced fibrosis and cirrhosis (F ≥ 3 and F4, respectively)]; b) non-invasive indexes [FIB-4, APRI, and their cut-offs (FIB-4 ≥ 3.25 and APRI≥1.5)]; c) inflammation-related biomarkers (leptin, HGF, NGF, sFasL, sFas, MIF, HA, Ang-2, TIMP1, MMP1 and MMP2).
Higher TIMP-1 and HA serum levels, and an ELF cut-off score of 8 were found to be correlated with the grade of liver fibrosis; these values may, therefore, assist physicians in identifying individuals at greater risk of disease.
In liver fibrogenesis, AT-II is known to stimulate proliferation and production of tissue inhibitor of metalloproteinases-1 (TIMP-1) in activated hepatic stellate cells (Ac-HSC), which play a pivotal role in liver fibrosis development.
In addition, transforming growth factor (TGF)-β, collagen I-α1, tissue inhibitor of metalloproteinase 1 (TIMP-1) and α-smooth muscle actin (SMA) mRNA expression, which are markers of hepatic fibrosis, were markedly inhibited by EGCG treatment.
Treatment with fasudil or captopril suppressed not only the inflammation reaction but also the accumulation of the extracellular matrix due to the downregulation of TGF-β1 and MMP-9/TIMP-1, which induces the amelioration of the liver fibrosis with diabetes.
This antifibrotic effect was associated to the decrease of fibrogenic markers involved in liver fibrosis progression, such as the transforming growth factor (TGF-<i>β</i>), the <i>α</i>-smooth muscle actin (α-SMA), and the tissue metalloproteinases inhibitor (TIMP-1).