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Expression of the insulin-like growth factor-II/mannose-6-phosphate receptor in multiple human tissues during fetal
B Funk1, U Kessler, W Eisenmenger
1Department of Pediatric Endocrinology, Childrens Hospital, Munich, Germany.
Insights
The human insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is present in all studied tissues, with highest expression in heart, thymus, and kidney. Developmental regulation shows a trend towards higher fetal expression, though not statistically significant.
Area of Science:
- Biochemistry
- Developmental Biology
- Molecular Biology
Background:
- The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is crucial for cellular processes.
- Previous studies in rats indicated significant developmental regulation of IGF-II/M6P receptor expression.
- Understanding human IGF-II/M6P receptor expression is vital for developmental studies.
Purpose of the Study:
- To investigate the differential expression of the human IGF-II/M6P receptor across various organs.
- To determine if the human IGF-II/M6P receptor exhibits developmental regulation from fetal to early postnatal stages.
- To analyze the expression patterns of IGF-binding proteins (IGFBPs) in human fetal and early postnatal tissues.
Main Methods:
- Protein extraction from human fetal and infant tissues (23 weeks gestation to 24 months postnatal) using SDS and Triton X-100 buffers.
- Analysis of protein extracts via SDS-PAGE and immunoblotting with anti-IGF-II/M6P receptor antiserum.
- Immunoquantitation using 125I-protein A and Western ligand blotting with 125I-IGF-II to assess receptor and IGFBP levels.
Main Results:
- IGF-II/M6P receptor immunoreactivity was detected in all examined human tissues.
- Highest receptor expression was observed in heart, thymus, and kidney; lowest in brain and muscle.
- A trend towards higher receptor levels in fetal tissues compared to postnatal tissues was noted, but differences were not statistically significant. Molecular weight variations were observed in brain tissue.
- Differential expression of IGFBP species was also observed across various organs.
Conclusions:
- The human IGF-II/M6P receptor is ubiquitously expressed, with organ-specific variations.
- While a trend suggests developmental regulation, significant changes in IGF-II/M6P receptor levels from fetal to early postnatal stages were not confirmed in this study.
- IGF-binding proteins also show differential expression patterns in human development.
Abstract:
The insulin like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor has been detected in many cells and tissues. In the rat, there is a dramatic developmental regulation of IGF-II/M6P receptor expression, the receptor being high in fetal and neonatal tissues and declining thereafter. We have systematically studied the expression of the human IGF-II/M6P receptor protein in tissues from 10 human fetuses and infants (age 23 weeks gestation to 24 months postnatal). We have asked 1) whether there is differential expression among different organs, and 2) whether or not the human IGF-II/M6P receptor is developmentally regulated from 23 weeks gestation to 24 months postnatal. Protein was extracted from human tissues using a buffer containing 2% sodium dodecyl sulfate and 2% Triton X-100. Aliquots of the protein extracts were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using an anti-IGF-II/M6P receptor antiserum (no. 66416) and 125I-protein A or an immunoperoxidase stain. IGF-II/M6P receptor immunoreactivity was detected in all tissues studied with the highest amount of receptor being expressed in heart, thymus, and kidney and the lowest receptor content being measured in brain and muscle. The receptor content in ovary, testis, lung, and spleen was intermediate. The apparent molecular weight of the IGF-II/M6P receptor (220,000 kilos without reduction of disulfide bonds) varied among the different tissues: in brain the receptor was of lower molecular weight than in other organs. Immunoquantitation experiments employing 125I-protein A and protein extracts from human kidney at different ages revealed a small, albeit not significant, difference of the receptor content between fetal and postnatal tissues: as in other species, larger amounts of receptor seemed to be present in fetal than in postnatal organs. In addition, no significant difference of the receptor content between human fetal liver and early postnatal liver was measured employing 125I-protein A-immunoquantitation in three fetal and five postnatal liver tissue samples. The distribution of IGF-binding protein (IGEBP) species, another abundant and major class of IGF binding principles, was also measured in human fetal and early postnatal lung, liver, kidney, muscle, and brain using Western ligand blotting with 125I-IGF-II: as with IGF-II/M6P receptor immunoreactivity there was differential expression of the different classes of IGFBPs in the various organs.(ABSTRACT TRUNCATED AT 400 WORDS)