INVESTIGADORES
HONORE Stella Maris
artículos
Título:
Hepatic fibrogenesis and TGF/Smad signaling activation in rats exposed to low doses of lead
Autor/es:
PEREZ AGUILAR R. C.*; HONORÉ S. M.* (AMBOS PRIMER AUTOR); GENTA S. B.; SANCHEZ S. S.
Revista:
JOURNAL OF APPLIED TOXICOLOGY
Editorial:
JOHN WILEY & SONS LTD
Referencias:
Lugar: Londres; Año: 2014 vol. 34 p. 1320 - 1331
ISSN:
0260-437X
Resumen:
Lead is an important heavy metal pollutant in the environment. The nervous system, kidney and liver are the most susceptible organs to lead deposition, showing that this pollutant has no single target system. To examine the cellular and molecular mechanisms involved in their pathobiology of chronic lead at low-dose exposure in the liver, male Wistar rats were exposed to 0.06% lead acetate in drinking water every day for 4 months. At the end of the study, hepatic metal accumulation, morphology and function were examined. Immunochemical staining and Western blot analysis were performed to detect extracellular matrix proteins, alpha-smooth muscle actin and transforming growth factor (TGF)b1/Smad pathway expression. Results showed increased laminin, collagen IV and fibronectin, located at the perisinusoidal space. Phenotypic transformation of hepatic stellate cells into myofibroblast-like cells was evidenced at the ultrastructural level and a significant expression of alpha-smooth muscle actin in Disse?s space was observed. These findings were associated with a marked increase in TGFb1/Smad2/3 signaling. Our data suggest that, chronically, exposure to low levels of lead could trigger the onset of a hepatic fibrogenic process through upregulated TGFb1/Smad signaling.