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Imprinted mesodermal specific transcript (MEST) and H19 genes in renal development and diabetes.
Yashpal S Kanwar1, Xiaomin Pan, Sun Lin
1Departments of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA. y-kanwar@northwestern.edu
Kidney International
|April 5, 2003
Summary
Expression of imprinted genes MEST and H19 decreases in embryonic kidneys under high glucose conditions, potentially causing developmental abnormalities. This finding challenges existing models of imprinted gene regulation during embryogenesis.
Area of Science:
- Developmental Biology
- Genetics
- Reproductive Biology
Background:
- Imprinted genes, mesodermal specific cDNA or transcript (MEST) and H19, are crucial for peri-implantation embryogenesis.
- Their expression patterns were investigated in embryonic kidneys experiencing glucose-induced developmental issues.
Purpose of the Study:
- To assess the expression of MEST and H19 imprinted genes in embryonic kidneys under hyperglycemic conditions.
- To investigate the role of these genes in glucose-induced kidney dysmorphogenesis.
Main Methods:
- Northern blot analysis for MEST and H19 mRNA expression in embryonic kidneys.
- Isolation and expression of MEST cDNA to generate antibodies for protein assessment via immunoprecipitation and immunofluorescence.
- Competitive RT-PCR and in situ tissue autoradiography to evaluate MEST and H19 mRNA expression in high glucose-treated explants.
Main Results:
- High expression of MEST and H19 observed in fetal kidneys, decreasing with gestation and undetectable postnatally.
- MEST and H19 expression decreased in embryonic kidneys exposed to high glucose and in fetuses from diabetic mothers.
- MEST protein expression shifted from mesenchyme to epithelial and ureteric bud elements and decreased in glucose-treated explants.
Conclusions:
- MEST and H19 are developmentally regulated in the mammalian embryonic kidney.
- Their decreased expression in high glucose or diabetic states deviates from established imprinted gene regulation dogma.
- This downregulation may disrupt epithelial-mesenchymal interactions, leading to kidney dysmorphogenesis.