Journal
JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
Volume 1, Issue 1, Pages 67-74Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S2040174409990134
Keywords
ERK signaling; gestational programming; maternal under-nutrition; nephrogenesis; nephropenia
Categories
Funding
- SMFM-AAOGF
- NIH [R03HD060782]
Ask authors/readers for more resources
Maternal under-nutrition (MUN) during gestation results in growth-restricted newborns with reduced glomerular number and subsequent hypertension. We investigated dysregulation of glial derived neurotrophic factor (GDNF) and MAPK-ERK (mitogen-activated protein kinase-extracellular signal-regulated protein kinase) signal pathway gene expression following MUN. MUN rats were 50% food restricted from embryonic day 10 till postnatal day 1. Kidneys were harvested at embryonic day (E) 20, and postnatal days (P) 1 and 21. Kidney protein expression was determined by Western blot. At E20, protein expression of growth factor receptor alpha 1 (GFR alpha 1) and phosphorylated ERK1/2 and mitogen-activated protein kinase kinase (MEK) 1/2 were reduced significantly, and immunohistochemistry confirmed reduction of phosphorylated ERK (pERK) with maintenance of pERK localization. Total MEK and ERK were unchanged. At P1, only GFR alpha 1 and pERK1/2 were reduced significantly while at P21, expression of all growth factors except total MEK was unchanged. Total MEK was increased. Glomerular number was decreased by 19% in P21 kidneys and blood pressure was increased in 12-week-old rats. In conclusion, GDNF and MAPK-ERK signaling are dysregulated during active nephrogenesis in fetal and early newborn offspring kidneys in the MUN model. This may be a key mechanism in reduced offspring nephrogenesis and programmed hypertension.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available