Epidermal growth factor receptor ligands in murine models for erythropoietic protoporphyria: potential novel players in the progression of liver injury
Fecha
2009Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión publicada / Argitaratu den bertsioa
Impacto
|
10.1170/T835 (DOI erróneo)
Resumen
Activation of the epidermal growth factor receptor (EGFR) plays an important role in liver regeneration and
resistance to acute injury. However its chronic activation participates in the progression of liver disease, including
fibrogenesis and malignant transformation. Hepatobiliary disease represents a constant feature in the clinically relevant
Fechm1pas/Fechm1pas genetic model of erythropoi ...
[++]
Activation of the epidermal growth factor receptor (EGFR) plays an important role in liver regeneration and
resistance to acute injury. However its chronic activation participates in the progression of liver disease, including
fibrogenesis and malignant transformation. Hepatobiliary disease represents a constant feature in the clinically relevant
Fechm1pas/Fechm1pas genetic model of erythropoietic protoporphyria (EPP). Similarly, chronic administration of griseofulvin
to mice induces pathological changes similar to those found in patients with EPP-associated liver injury. We investigated the
hepatic expression of the EGFR and its seven most relevant ligands in Fechm1pas/Fechm1pas mice bred in three different
backgrounds, and in griseofulvin-induced protoporphyria. We observed that the expression of amphiregulin, betacellulin and
epiregulin was significantly increased in young EPP mice when compared to aged-matched controls in all genetic
backgrounds. The expression of these ligands was also tested in older (11 months) BALB/cJ EPP mice, and it was found to
remain induced, while that of the EGFR was downregulated. Griseofulvin feeding also increased the expression of
amphiregulin, betacellulin and epiregulin. Interestingly, protoporphyrin accumulation in cultured hepatic AML-12 cells
readily elicited the expression of these three EGFR ligands. Our findings suggest that protoporphyrin could directly induce
the hepatic expression of EGFR ligands, and that their chronic upregulation might participate in the pathogenesis of EPPassociated
liver disease. [--]
Materias
Erythropoietic protoporphyria,
Protoporphyrin,
Hepatobiliary disease,
Amphiregulin,
Betacellulin,
Epiregulin,
Epidermal growth factor receptor
Editor
CMB Association
Publicado en
Cellular and Molecular Biology 2009, 55(1), 29-37
Departamento
Universidad Pública de Navarra. Departamento de Ciencias de la Salud /
Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila
Versión del editor
Entidades Financiadoras
Work in the authors’ laboratory is supported by: the agreement between FIMA and the “UTE project CIMA”; Spanish Fundación Mutua Madrileña (to AF, CB, RES, FJC and MAA); Red Temática de Investigación Cooperativa en Cáncer RD06 00200061 (to CB, FJC and MAA), and CIBERehd (to JP) from Instituto de Salud Carlos III; Grants from Ministerio de Sanidad y Consumo FIS PI070392 and PI070402 (to CB and MAA); FIS PI 061475 (to AF) and FIS PI 02/1888 (to RES, AF and MGB); Grant SAF2008-0154 from Ministerio de Educación y Ciencia (to FJC). MUL and SG were supported by a Juan de la Cierva contract from MEC, and a fellowship from FIS respectively.