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An expression of IGF-binding proteins in normal and pre-eclamptic human umbilical cord serum and tissues
Edward Bańkowski1, Jerzy Pałka, Stefan Jaworski
1Department of Medical Biochemistry, Medical Academy of Białystok, Poland. edward@amb.edu.pl
Insights
Pre-eclampsia alters insulin-like growth factor-I binding proteins (BPs) in umbilical cord arteries, affecting extracellular matrix production. These BP changes may influence fetal development in pre-eclamptic pregnancies.
Area of Science:
- Reproductive Biology
- Endocrinology
- Biochemistry
Background:
- Pre-eclampsia is a common pregnancy disorder associated with increased collagen and glycosaminoglycans in umbilical cord arteries.
- Insulin-like growth factor-I (IGF-I) promotes fetal tissue growth and extracellular matrix synthesis.
- IGF-I activity is modulated by IGF-binding proteins (BPs).
Purpose of the Study:
- To investigate differences in IGF-binding proteins (BPs) between normal and pre-eclamptic human umbilical cord tissues and sera.
- To explore the role of BPs in modulating IGF-I action in the context of pre-eclampsia.
Main Methods:
- Western immunoblot analysis to detect and characterize IGF-binding proteins (BPs) in umbilical cord (UC) serum, UCA-wall, and Wharton's jelly.
- Ligand binding assays to assess IGF-I binding to BPs.
- Assays to evaluate the degradation of IGF-I-BP complexes.
Main Results:
- Qualitative differences in BP profiles were observed between normal and pre-eclamptic samples.
- Pre-eclamptic umbilical cord arteries (UCAs) and Wharton's jelly showed distinct lower molecular weight BP-3-reactive material.
- IGF-I binding patterns varied, with less binding in pre-eclamptic serum and more in pre-eclamptic UCAs.
- Both normal and pre-eclamptic tissues degraded IGF-I-BP complexes, potentially increasing free IGF-I.
Conclusions:
- Specific IGF-binding proteins (BPs) and their proteolytic modifications in umbilical cord tissues are altered in pre-eclampsia.
- These alterations may modulate insulin-like growth factor-I (IGF-I) action, influencing extracellular matrix production.
- BP modifications could contribute to the pathological changes observed in pre-eclamptic pregnancies.
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.