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Expression profiles of congenital renal dysplasia reveal new insights into renal development and disease.
- Source :
-
Pediatric nephrology (Berlin, Germany) [Pediatr Nephrol] 2007 Jul; Vol. 22 (7), pp. 962-74. Date of Electronic Publication: 2007 Apr 21. - Publication Year :
- 2007
-
Abstract
- Congenital renal dysplasia (RD) is a major cause of renal failure in the pediatric population. Although molecular and genetic aspects of RD have been studied in animal models, limited studies have been done in human RD primarily due to lack of available material. To identify novel genes that are associated with RD and normal kidney development, we performed microarray analysis on total RNA extracted from age-matched fetal kidneys of normal and RD patients. In midgestational RD kidneys, we found 180 upregulated and 104 downregulated transcripts compared with normal kidneys. Among the increased transcripts in the dysplastic kidneys were matrix-degrading enzymes (MMP7, MMP19, TIMP1), inflammation- and immunity-related genes, and growth factors. Expression of genes known to be essential for normal kidney development, such as WT1, BMP7, renin, angiotensin receptor 2 (AGTR2), SAL-like 1 (SALL1) and glypican 3 (GPC3), were decreased in dysplastic kidneys. Expression of selected gene products (BMP7, renin, and MMP7) was further confirmed in parallel sections and in several normal and human dysplastic kidneys, supporting the role of these genes as putative RD biomarkers. These results are among the first to reveal disrupted expression profiles during gestation in human RD patients.
- Subjects :
- Bone Morphogenetic Protein 7
Bone Morphogenetic Proteins genetics
Bone Morphogenetic Proteins metabolism
Case-Control Studies
Fetus
Gestational Age
Humans
Immunohistochemistry
Kidney Diseases, Cystic pathology
Matrix Metalloproteinase 7 genetics
Matrix Metalloproteinase 7 metabolism
Oligonucleotide Array Sequence Analysis
Renin genetics
Renin metabolism
Gene Expression
Kidney growth & development
Kidney Diseases, Cystic embryology
Kidney Diseases, Cystic genetics
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 0931-041X
- Volume :
- 22
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Pediatric nephrology (Berlin, Germany)
- Publication Type :
- Academic Journal
- Accession number :
- 17450386
- Full Text :
- https://doi.org/10.1007/s00467-007-0466-6