title: An expression of IGF-binding proteins in normal and pre-eclamptic human umbilical cord serum and tissues.
abstract: Pre-eclampsia, is the most common, pregnancy-associated pathological syndrome accompanied by a significant increase in collagen and sulphated glycosaminoglycans (GAGs) contents in the umbilical cord arteries (UCAs). Insulin-like growth factor-I (IGF-I) is expressed in most foetal tissues and it is involved in anabolic effects. It stimulates protein (mainly collagen) and GAG biosynthesis, cell proliferation and differentiation. Previously, we have found that pre-eclampsia is associated with an increase of IGF-I concentration in the umbilical cord blood. A family of IGF-I-binding proteins (BPs) modulates the activity of IGF-I. We demonstrated qualitative differences between BPs of normal and pre-eclamptic human umbilical cord (UC) serum and UC-tissues (UCA-wall and Wharton's jelly) by Western immunoblot analysis. All examined sera and tissues contained BP-1 and BP-5 as well lower molecular weight materials. The BP-2 was recovered from both control and pre-eclamptic sera, while it was not detected in the UC-tissues. Instead, lower molecular weight forms of BP-2 were found as judged by the anti-BP-2 antibody. The BP-3 was detected in sera, UCA and Wharton's jelly. The most distinct expression of BP-3 was found in the UCA. The pre-eclamptic UCA and Wharton's jelly contained additional BP-3-reactive material of lower molecular weight. The BP-4 was strongly expressed in pre-eclamptic UC-serum and the expression was decreased in pre-eclamptic UC-tissues, compared to respective controls. Ligand binding assay revealed that most of IGF-I was bound to 46 kDa region (typical for BP-3) in both control and pre-eclamptic sera and tissues. However, distinctly less IGF-I was bound in pre-eclamptic serum, distinctly more in pre-eclamptic UCA and no differences were found in pre-eclamptic Wharton's jelly, compared to controls. We demonstrated that both normal and pre-eclamptic UC-sera and tissues are able to degrade 46 kDa IGF-I-BP. The degradation may result in a decrease of IGF-I binding, contributing to increase in free IGF-I that may stimulate the cells to produce extracellular matrix (ECM) components. The specific BPs and their proteolytic modification in UC tissues may be important modulators of IGF-I action during foetal development.
authors.affiliation: Department of Medical Biochemistry, Medical Academy of Białystok, Poland. edward@amb.edu.pl
authors.forename: Edward
authors.initials: E
authors.lastname: Bańkowski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Pałka
authors.forename: Stefan
authors.initials: S
authors.lastname: Jaworski
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000096:biosynthesis*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000378:metabolism; D008024:Ligands; D011225:Pre-Eclampsia / Q000378:metabolism*; D011233:Precipitin Tests; D011247:Pregnancy; D011485:Protein Binding; D013696:Temperature; D014018:Tissue Distribution; D014470:Umbilical Cord / Q000378:metabolism*
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D008024:Ligands; D007334:Insulin-Like Growth Factor I