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D-glucose-induced dysmorphogenesis of embryonic kidney
1Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
The Journal of Clinical Investigation
|December 1, 1996
Summary
High glucose levels impair embryonic kidney development by reducing perlecan, a key protein. This disruption affects cell growth and survival, leading to kidney malformations.
Area of Science:
- Developmental Biology
- Molecular Biology
- Biochemistry
Background:
- Embryonic kidney development (metanephrogenesis) is crucial for renal function.
- Dysmorphogenesis can lead to congenital kidney diseases.
- The role of glucose in kidney development is not fully understood.
Purpose of the Study:
- To investigate the effects of D-glucose on embryonic kidney development in vitro.
- To elucidate the molecular mechanisms underlying D-glucose-induced kidney dysmorphogenesis.
Main Methods:
- Organ culture of embryonic kidneys (metanephroi) with 30 mM D-glucose.
- Assessment of nephron size, cell population, and morphology.
- Analysis of perlecan expression using RT-PCR and immunoprecipitation.
- Evaluation of activated protein-2 binding activity and phosphorylation.
- Measurement of cellular ATP levels.
- ATP administration to assess rescue effects.
Main Results:
- D-glucose significantly reduced nephron size and population.
- Ureteric bud branching was impaired, and metanephric mesenchyme showed atrophy, reduced proliferation, and increased apoptosis.
- Perlecan expression and activated protein-2 binding activity were decreased.
- Cellular ATP levels were reduced in D-glucose-treated explants.
- Exogenous ATP restored normal metanephric morphology and perlecan levels.
Conclusions:
- D-glucose adversely affects metanephrogenesis by disrupting phosphorylation events crucial for perlecan regulation.
- Reduced perlecan impairs epithelial/mesenchymal interactions, leading to kidney dysmorphogenesis and mesenchyme apoptosis.
- These findings highlight a potential mechanism for diabetic embryopathy affecting kidney development.
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