Involvement of hepatic stellate cells and TGF/Smad signaling in liver fibrogenesis induced by lead

PEREZ AGUILAR R.C.; HONORÉ S.M.; GENTA S.B; SÁNCHEZ S. S.

ARCHIVES OF TOXICOLOGY.

SPRINGER

Año: 2012 p. 1 - 27

0340-5761

Lead is an important heavy metal pollutant in the environment, primarily as the result of anthropogenic activities. The nervous system, kidney and liver are the most susceptible organs to lead deposition showing that this pollutant has no single target system. Although morphological and functional alterations in these organs have been highlighted, cellular and molecular mechanisms involved in its pathobiology are not fully understand. Using a rat model of long term lead acetate exposure (0.06% lead acetate in drinking water) we report that low levels of lead induce a significant increase of the extracellular proteins laminin, collagen IV and fibronectin, localized at the perisinusoidal space. Moreover, phenotypic transformation of hepatic stellate cells into myofibroblast-like cells is evidenced at ultrastructural level. A significant expression of alpha-smooth muscle actin (alpha-SMA) in the liver parenchyma particularly Disse’s space is also observed. These changes indicated an activation of quiescent hepatic stellate cells. Furthermore, we determined that TGFbeta1 signaling pathway is involved in the toxic action of lead. In conclussion, low levels of lead exposure induce a phenotipic change of stellate cells, increase the synthesis of extracellular matrix in the liver and up-regulate TGFbeta1/Smad signaling. Lead triggered alterations are associated with the onset a fibrogenic process