Back to Search
Start Over
Ex vivo modeling of chemical synergy in prenatal kidney cystogenesis.
- Source :
-
PloS one [PLoS One] 2013; Vol. 8 (3), pp. e57797. Date of Electronic Publication: 2013 Mar 12. - Publication Year :
- 2013
-
Abstract
- Cyclic adenosine monophosphate (cAMP) drives genetic polycystic kidney disease (PKD) cystogenesis. Yet within certain PKD families, striking differences in disease severity exist between affected individuals, and genomic and/or environmental modifying factors have been evoked to explain these observations. We hypothesized that PKD cystogenesis is accentuated by an aberrant fetal milieu, specifically by glucocorticoids. The extent and nature of cystogenesis was assessed in explanted wild-type mouse embryonic metanephroi, using 8-Br-cAMP as a chemical to mimic genetic PKD and the glucocorticoid dexamethasone as the environmental modulator. Cysts and glomeruli were quantified by an observer blinded to culture conditions, and tubules were phenotyped using specific markers. Dexamethasone or 8-Br-cAMP applied on their own produced cysts predominantly arising in proximal tubules and descending limbs of loops of Henle. When applied together, however, dexamethasone over a wide concentration range synergized with 8-Br-cAMP to generate a more severe, glomerulocystic, phenotype; we note that prominent glomerular cysts have been reported in autosomal dominant PKD fetal kidneys. Our data support the idea that an adverse antenatal environment exacerbates renal cystogenesis.
- Subjects :
- 8-Bromo Cyclic Adenosine Monophosphate adverse effects
8-Bromo Cyclic Adenosine Monophosphate pharmacology
Animals
Dexamethasone adverse effects
Dexamethasone pharmacology
Female
Fetus pathology
Glucocorticoids adverse effects
Glucocorticoids pharmacology
Kidney pathology
Male
Mice
Polycystic Kidney Diseases chemically induced
Polycystic Kidney Diseases pathology
Pregnancy
Fetus embryology
Kidney embryology
Models, Biological
Polycystic Kidney Diseases embryology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23554868
- Full Text :
- https://doi.org/10.1371/journal.pone.0057797