Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis

• Author(s): Duarte, T. ; Caldas, C. ; Santos, A. ; Silva-Gomes, S. ; Santos-Gonçalves, A. ; Martins, M. ; Porto, G. ; Lopes, J.
• Date: 2017
• Persistent ID: http://hdl.handle.net/10400.16/2180
• Origin: Repositório Científico da Unidade Local de Saúde de Santo António (ULSSA)
• Subject(s): Hepatocyte; Iron; Macrophage; Oxidative stress; Sideronecrosis
• Document Type: Journal article
• Language: English
• Contributor(s): Repositório Científico da Unidade Local de Saúde de Santo António

Description

In hereditary hemochromatosis, iron deposition in the liver parenchyma may lead to fibrosis, cirrhosis and hepatocellular carcinoma. Most cases are ascribed to a common mutation in the HFE gene, but the extent of clinical expression is greatly influenced by the combined action of yet unidentified genetic and/or environmental modifying factors. In mice, transcription factor NRF2 is a critical determinant of hepatocyte viability during exposure to acute dietary iron overload. We evaluated if the genetic disruption of Nrf2 would prompt the development of liver damage in Hfe(-/-) mice (an established model of human HFE-hemochromatosis).