TY - JOUR N2 - 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. ID - discovery1511670 UR - http://doi.org/10.1074/jbc.M611315200 SN - 1083-351X JF - Journal of Biological Chemistry A1 - Moretti, FA A1 - Chauhan, AK A1 - Iaconcig, A A1 - Porro, F A1 - Baralle, FE A1 - Muro, AF TI - A Major Fraction of Fibronectin Present in the Extracellular Matrix of Tissues Is Plasma-derived AV - public VL - 282 Y1 - 2007/09/21/ SP - 28057 EP - 28062 IS - 38 N1 - This version is the version of record. For information on re-use, please refer to the publisher?s terms and conditions. ER -