Expression profiles of congenital renal dysplasia reveal new insights into renal development and disease.
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.
Jain
Sanjay
S
Department of Medicine (Renal Division), Washington University School of Medicine, Saint Louis, MO, 63110, USA.
Suarez
Adrian A
AA
McGuire
John
J
Liapis
Helen
H
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D005333:Fetus; D015870:Gene Expression; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000254:growth & development*; D052177:Kidney Diseases, Cystic / Q000196:embryology* / Q000235:genetics* / Q000473:pathology; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012083:Renin / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D012083:Renin; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7