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)

Exposure to oxalate, a constituent of the most common form of kidney stones, generates toxic responses in renal epithelial cells, including altered membrane surface properties and cellular lipids, changes in gene expression, disruption of mitochondrial function, formation of reactive oxygen species and decreased cell viability. Oxalate exposure activates phospholipase A2 (PLA2), which increases two lipid signaling molecules, arachidonic acid and lysophosphatidylcholine (Lyso-PC). PLA2 inhibition blocks, whereas exogenous Lyso-PC or arachidonic acid reproduce many of the effects of oxalate on mitochondrial function, gene expression and cell viability, suggesting that PLA2 activation plays a role in mediating oxalate toxicity. Oxalate exposure also elicits potentially adaptive or protective changes that increase expression of proteins that may prevent crystal formation or attachment. Additional adaptive responses may facilitate removal and replacement of dead or damaged cells. The presence of different inflammatory cells and molecules in the kidneys of rats with hyperoxaluria and in stone patients suggests that inflammatory responses play roles in stone disease. Renal epithelial cells can synthesize a variety of cytokines, chemoattractants and other molecules with the potential to interface with inflammatory cells; moreover, oxalate exposure increases the synthesis of these molecules. The present studies demonstrate that oxalate exposure upregulates cyclooxygenase-2, which catalyzes the rate-limiting step in the synthesis of prostanoids, compounds derived from arachidonic acid that can modify crystal binding and may also influence inflammation. In addition, renal cell oxalate exposure promotes rapid degradation of IkappaBalpha, an endogenous inhibitor of the NF-kappaB transcription factor. A similar response is observed following renal cell exposure to lipopolysaccharide (LPS), a bacterial cell wall component that activates toll-like receptor 4 (TLR4). While TLRs are primarily associated with immune cells, they are also found on many other cell types, including renal epithelial cells, suggesting that TLR signaling could directly impact renal function. Prior exposure of renal epithelial cells to oxalate in vitro produces endotoxin tolerance, i.e. a loss of responsiveness to LPS and conversely, prior exposure to LPS elicits a similar heterologous desensitization to oxalate. Renal cell desensitization to oxalate stimulation may have profound effects on the outcome of renal stone disease by impairing protective responses.
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PMID:Oxalate toxicity in renal cells. 1628 83

Hyperoxaluria-induced calcium oxalate (CaOx) deposition is the key factor in kidney stone formation, for which adipose-derived stromal cells (ADSCs) have been used as a therapeutic treatment. Studies revealed that miR-20b-3p is down-regulated in hypercalciuric stone-forming rat kidney. To investigate whether ADSC-derived miR-20b-3p-enriched exosomes protect against kidney stones, an ethylene glycol (EG)-induced hyperoxaluria rat model and an in vitro model of oxalate-induced NRK-52E cells were established to explore the protective mechanism of miR-20b-3p. The results showed that miR-20b-3p levels were decreased following hyperoxaluria in the urine of patients and in kidney tissues from animal models. Furthermore, treatment with miR-20b-3p-enriched exosomes from ADSCs protected EG-induced hyperoxaluria rats, and cell experiments confirmed that co-culture with miR-20b-3p-enriched exosomes alleviated oxalate-induced cell autophagy and the inflammatory response by inhibiting ATG7 and TLR4. In conclusion, ADSC-derived miR-20b-3p-enriched exosomes protected against kidney stones by suppressing autophagy and inflammatory responses.
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PMID:Exosomes from miR-20b-3p-overexpressing stromal cells ameliorate calcium oxalate deposition in rat kidney. 3168 50