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To examine the cellular and molecular mechanisms involved in their pathobiology of chronic lead at low\u2010dose 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, \u03b1\u2010smooth muscle actin and transforming growth factor (TGF)\u03b21\/Smad pathway expression. Results showed increased laminin, collagen IV and fibronectin, located at the perisinusoidal space. Phenotypic transformation of hepatic stellate cells into myofibroblast\u2010like cells was evidenced at the ultrastructural level and a significant expression of \u03b1\u2010smooth muscle actin in Disse's space was observed. These findings were associated with a marked increase in TGF\u03b21\/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 TGF\u03b21\/Smad signaling. Copyright \u00a9 2013 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.2955","type":"journal-article","created":{"date-parts":[[2013,11,6]],"date-time":"2013-11-06T03:38:52Z","timestamp":1383709132000},"page":"1320-1331","source":"Crossref","is-referenced-by-count":9,"title":["Hepatic fibrogenesis and transforming growth factor\/Smad signaling activation in rats chronically exposed to low doses of lead"],"prefix":"10.1002","volume":"34","author":[{"given":"Rossana C.","family":"Perez Aguilar","sequence":"first","affiliation":[{"name":"Dpto. 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