Evidence for the involvement of TGF-beta1-CTGF axis in liver fibrogenesis secondary to hepatic viral infection

摘要

Liver fibrosis is a nonspecific response to injuries, which implies the synthesis of an abnormal extracellular matrix (ECM). TGF-beta (transforming growth factor beta) is a cytokine involved in regulation of several important processes: cell development and differentiation, apoptosis, synthesis and degradation of ECM. CTGF (connective tissue growth factor) is a cysteine rich peptide that belongs to the CCN family of proteins and plays an essential role in the formation of blood vessels, bone and connective tissue. The purpose of this study was to assess TGF-beta1 and CTGF immunohistochemical expression in different stages of liver fibrosis secondary to chronic viral hepatitis. Liver biopsies from patients diagnosed with chronic viral hepatitis B and C were embedded in paraffin and further used for histological staining and immunohistochemical reactions to detect TGF-beta1 and CTGF. Liver sections stained with trichromic Masson for collagen staining and Gomori's silver impregnation revealed various degrees of liver fibrosis, noted in the METAVIR scale from 1 to 4. Sections with discrete degrees of fibrosis revealed the positivity only in the endothelial cells of liver sinusoids and occasionally in proinflammatory cells from the portal tracts, the number of TGF-beta1-positive cells being directly proportional to the incidence of liver injury. Positive reaction for TGF-beta1 expanded to the cytoplasm of hepatocytes located nearby fibrosis bundles while increasing the parenchymal damage. The expression of CTGF was observed in the classical areas of the hepatic lobule, such as the perisinusoidal spaces around the portal tracts or central veins, but also in the hepatocytes surrounding the fibrotic areas. Regardless of the etiological factor of liver damage, activation of liver cells causes an increased synthesis of TGF-beta1 followed by a CTGF overproduction in various polymorphic hepatic structures, in accordance with the degree of fibrosis.