title: Hepatic fibronectin matrix turnover in rats: involvement of the asialoglycoprotein receptor.
abstract: Fibronectin (Fn) is a major adhesive protein found in the hepatic extracellular matrix (ECM). In adult rats, the in vivo turnover of plasma Fn (pFn) incorporated into the liver ECM is relatively rapid, i.e., <24 h, but the regulation of its turnover has not been defined. We previously reported that cellular Fn (cFn) and enzymatically desialylated plasma Fn (aFn), both of which have a high density of exposed terminal galactose residues, rapidly interact with hepatic asialoglycoprotein receptors (ASGP-R) in association with their plasma clearance after intravenous infusion. With the use of adult male rats (250-350 g) and measurement of the deoxycholate (DOC)-insoluble (125)I-labeled Fn in the liver, we determined whether the ASGP-R system can also influence the hepatic matrix retention of various forms of Fn. There was a rapid deposition of (125)I-pFn, (125)I-aFn, and (125)I-cFn into the liver ECM after their intravenous injection. Although (125)I-pFn was slowly lost from the liver matrix over 24 h, more than 90% of the incorporated (125)I-aFn and (125)I-cFn was cleared within 4 h (P < 0.01). Intravenous infusion of excess nonlabeled asialofetuin to competitively inhibit the hepatic ASGP-R delayed the rapid turnover of both aFn and cFn already incorporated within the ECM of the liver. ECM retention of both (125)I-aFn and (125)I-cFn was also less than (125)I-pFn (P < 0.01) as determined in vitro using liver slices preloaded in vivo with either tracer form of Fn. The hepatic ASGP-R appears to participate in the turnover of aFn and cFn within the liver ECM, whereas a non-ASGP-R-associated endocytic pathway apparently influences the removal of normal pFn incorporated within the hepatic ECM, unless it becomes locally desialylated.
authors.affiliation: Department of Physiology and Cell Biology, Albany Medical College, Albany, New York 12208, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Rotundo
authors.forename: P A
authors.initials: PA
authors.lastname: Vincent
authors.forename: P J
authors.initials: PJ
authors.lastname: McKeown-Longo
authors.forename: F A
authors.initials: FA
authors.lastname: Blumenstock
authors.forename: T M
authors.initials: TM
authors.lastname: Saba
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000302:isolation & purification / Q000378:metabolism / Q000493:pharmacokinetics; D002458:Cell Fractionation; D002738:Chloroquine / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000378:metabolism / Q000493:pharmacokinetics; D003840:Deoxycholic Acid; D003902:Detergents; D004705:Endocytosis / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D060748:Fetuins; D005347:Fibroblasts / Q000737:chemistry; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D005690:Galactose / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D007536:Isomerism; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000509:alpha-Fetoproteins / Q000302:isolation & purification / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D018501:Antirheumatic Agents; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D003432:Cross-Linking Reagents; D003902:Detergents; D016326:Extracellular Matrix Proteins; D060748:Fetuins; D005353:Fibronectins; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D000509:alpha-Fetoproteins; C017029:asialofetuin; D003840:Deoxycholic Acid; D002738:Chloroquine; D005690:Galactose