Effects of specific genes activating RAGE on polycystic kidney disease.
BACKGROUND
Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation and secretion of fluid and is associated with interstitial inflammation and fibrosis, resulting in the loss of renal function. We previously generated mice overexpressing PKD2, causing progressive cyst development with an inflammatory and fibrotic phenotype in the kidneys.


METHODS
To profile the gene expression related to inflammation and cystogenesis, microarray analysis was performed with kidney tissue from 6-, 12- and 18-month-old mice. Subsequently, levels and related mechanisms of selected genes, s100a8 and s100a9, were evaluated.


RESULTS
S100a8 and s100a9 was upregulated more than 2-fold and differently expressed in the cystic region. Receptor of advanced glycation end product (RAGE) is a putative cell surface receptor for s100a8/a9. It was expressed in cyst-lining cells and up-regulated pro-inflammatory transcription factor NF-kappaB in transgenic mice. We also confirmed RAGE expression in ADPKD patient kidneys. It was suggested that the signaling related to proliferative cystogenesis through previous reports; therefore, we confirmed that phosphorylated-ERK and cyst formation was reduced by treatment of RAGE-siRNA.


CONCLUSIONS
The results may provide important information for the expression of s100a8/a9 and RAGE, linking progressive cystogenesis with inflammation in cystic kidney.
Park
Eun Young
EY
Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
Seo
Min Ji
MJ
Park
Jong Hoon
JH
D000818:Animals; D040501:Calgranulin A / Q000096:biosynthesis / Q000235:genetics*; D040502:Calgranulin B / Q000096:biosynthesis / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism*; D015870:Gene Expression; D007249:Inflammation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007684:Kidney Tubules / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000378:metabolism / Q000473:pathology; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation
D040501:Calgranulin A; D040502:Calgranulin B; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C086145:S100a8 protein, mouse