Dispensability and dynamics of caveolin-1 during liver... : Hepatology (original) (raw)

Liver Injury/Regeneration

Dispensability and dynamics of caveolin-1 during liver regeneration and in isolated hepatic cells

Mayoral, Rafael1,2; Fernández-Martínez, Amalia1,2; Roy, Rosa1,2; Boscá, Lisardo1,2*; Martín-Sanz, Paloma1,2*

1 Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain

2 Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain

* Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Arturo Duperier 4, 28029 Madrid, Spain

Email:[email protected]

Received 28 November 2006; Accepted 27 March 2007

Published online in Wiley InterScience (www.interscience.wiley.com).

Grant sponsor: CNIC-BANCAJA fellowship; Grant Number: SAF2004-00957; Grant sponsor: Ministerio de Ciencia y Tecnologia; Grant Number: SAF2005-03022; Grant sponsor: Fundación Mutua Madrileña (Spain).

Potential conflict of interest: Nothing to report.

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Abstract

Caveolae participate in several cellular processes such as vesicular transport, cholesterol homeostasis, regulation of signal transduction, integrin signaling, and cell growth. The expression and functional role of caveolin (Cav), the most abundant protein of caveolae, has been reported in liver and in different hepatocyte cell lines, in human cirrhotic liver, and in hepatocellular carcinomas. The role of Cav-1 in liver regeneration after partial hepatectomy (PH) has been investigated as a model of liver proliferation in vivo . Our results show that Cav-1 increases in liver after PH with a redistribution of the protein from the caveola-enriched domain to the noncaveolar fraction. Moreover, the Cav-1 located in the noncaveolar fraction is phosphorylated in tyrosine 14, even though the Cav-1 gene is dispensable for liver regeneration after PH, as deduced from data obtained with commercially available animals lacking this gene. In addition to this, the proinflammatory stimulation of hepatocytes induces Cav-1 translocation to a noncaveolar fraction and tyrosine 14 phosphorylation mainly through the activation of tyrosine kinases such as Src. Conclusion: These results support a dynamic role for Cav-1 in liver proliferation both in vivo after PH and in vitro in cultured hepatic cell lines, but with minimal implications for the liver regeneration process. (Hepatology 2007.)

Abbreviations: bp, base pair; Cav, caveolin; EGF, epidermal growth factor; ER, endoplasmic reticulum; HGF, hepatocyte growth factor; IL-1β, interleukin-1β; NOS, nitric oxide synthase; PBS, phosphate-buffered saline; PCNA, proliferating cell nuclear antigen; PH, partial hepatectomy; PMSF, phenylmethylsulfonyl fluoride; SD, standard deviation; TNF-α, tumor necrosis factor α; Y14, tyrosine 14.