Lead-induced hepatic fibrogenesis

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

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Jornada; XXVIII Jornadas Científicas Asociación de Biología de Tucumán Tafí del Valle, Tucumán; 2011

Asociacion de Biologia de Tucumán

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 induces 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 TGF beta1 signaling pathway is involved in the toxic action of lead. In conclussion, low levels of lead exposition induces a phenotipic change of stellate cells, increasing the synthesis of extracellular matrix in the liver. Lead trigger alterations are associated with the onset a fibrogenic process.