Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020500 (hyperoxaluria)
 912 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary or secondary hyperoxaluria is associated with calcium oxalate nephrolithiasis, interstitial fibrosis and progressive renal insufficiency. Monolayer cultures of nontransformed monkey kidney epithelial cells (BSC-1 line) and calcium oxalate monohydrate (COM) crystals were used as a model system to study cell responses to crystal interactions that might occur in the nephrons of patients during periods of hyperoxaluria. To determine if COM crystals signal a change in gene expression, Northern blots were prepared from total renal cellular RNA after the cells were exposed to crystals. The immediate early genes c-myc, EGR-1, and Nur-77 were induced at one hour. At two to six hours stimulated expression of the genes encoding plasminogen activator inhibitor (PAI-1) and platelet-derived growth factor (PDGF)-A chain was detected, but constitutive expression of urokinase-type plasminogen activator (u-PA) was not altered. Expression of connective tissue growth factor (CTGF) was induced at one hour and persisted up to 24 hours. The stimulation of gene expression by COM crystals was relatively crystal- and renal cell-type specific. Thus the interaction of kidney epithelial cells with COM crystals alters expression of genes that encode three classes of proteins: transcriptional activators, a regulator of extracellular matrix (ECM), and growth factors. Activation of PAI-1 gene expression without a change in u-PA favors accumulation of ECM proteins, as does increased expression of PDGF and CTGF which can also stimulate fibroblast proliferation in a paracrine manner. These results suggest that COM crystal-mediated stimulation of specific genes in renal tubular cells may contribute to the development of interstitial fibrosis in hyperoxaluric states.
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PMID:Calcium oxalate monohydrate crystals stimulate gene expression in renal epithelial cells. 756 19

Experimental hyperoxaluria and calcium oxalate (CaOx) crystals are associated with renal epithelial injury and cell death. A recent study has demonstrated an oxalate-induced increase in cellular apoptosis in vitro, and speculates that this phenomenon may contribute to stone formation. We investigated the incidence of apoptotic cells and the expression of apoptosis related genes in the kidneys of stone-forming rats. Male Wistar rats were administrated ethylene glycol in drinking water and force fed with 1alpha-OH-D3. Apoptosis was detected as a ladder of fragmented DNA in agarose gels of electrophoresed genomic DNA. Apoptotic cells were localized by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. The expression of apoptosis-related genes was analyzed by both reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. While no labeling was detected in the controls or on the first day of administration by the TUNEL method, labeling began to be detected in the renal tubular epithelium of the outer medulla at day 3, and the number of labeled cells increased progressively during the observation period. A ladder of DNA fragments was demonstrated in the kidneys of rats after 2 weeks. Immunohistochemical studies revealed the expression of Fas ligand (Fas L), Bax and interleukin-1 beta converting enzyme (ICE) in the renal tubular epithelium of the descending limb of loop of Henle and the distal convoluted tubules. mRNA of the ICE, c-myc, p53 and Fas L genes was also upregulated in the kidneys of the stone-forming rats.
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PMID:Apoptosis and its related genes in renal epithelial cells of the stone-forming rat. 1523 56