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J. Biol. Chem., Vol. 282, Issue 38, 28057-28062, September 21, 2007
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From the International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy
The origin of the fibronectin (FN) found in the extracellular matrix of tissues has not been defined experimentally. Previous studies suggest that there is contribution from both local tissue production and transfer from plasma, but the extent of this phenomenon has not been addressed. We have shown before that engineered mice constitutively expressing extra domain A-containing FN (EDA+FN) have a significant decrease of FN levels in plasma and most tissues. We showed that hepatocytes modified to produce EDA+FN have normal extracellular matrix-FN levels but secrete less soluble FN. When we performed a liver-specific EDA-exon deletion in these animals, FN levels were restored both in plasma and tissues. Therefore, an important fraction of tissue FN, approximately an equal amount of that produced by the tissue itself, is actually plasma-derived, suggesting that plasma is an important source of tissue FN. The present results have potential significance for understanding the contributions of plasma FN, and perhaps other plasma proteins, in the modulation of cellular activities and in the formation of the extracellular matrix of tissues.
Received for publication, December 11, 2006 , and in revised form, May 9, 2007.
* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S3 and supplemental Materials and Methods.
1 Present Address: CBR Institute for Biomedical Research and Dept. of Pathology, Harvard Medical School, Boston, MA 02115.
2 To whom correspondence should be addressed: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I 34012, Trieste, Italy. Tel.: 39-040-3757312; Fax: 39-040-226555; E-mail: muro{at}icgeb.org.
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