PMID:17538188

Citation	Zhang, SL, Chen, YW, Tran, S, Chenier, I, Hébert, MJ and Ingelfinger, JR (2007) Reactive oxygen species in the presence of high glucose alter ureteric bud morphogenesis. J. Am. Soc. Nephrol. 18:2105-15
Abstract	Renal malformations are a major cause of childhood renal failure. During the development of the kidney, ureteric bud (UB) branching morphogenesis is critical for normal nephrogenesis. These studies investigated whether renal UB branching morphogenesis is altered by a high ambient glucose environment and studied underlying mechanism(s). Kidney explants that were isolated from different periods of gestation (embryonic days 12 to 18) from Hoxb7-green fluorescence protein mice were cultured for 24 h in either normal d-glucose (5 mM) or high d-glucose (25 mM) medium with or without various inhibitors. Alterations in renal morphogenesis were assessed by fluorescence microscopy. Paired-homeobox 2 (Pax-2) gene expression was determined by real-time quantitative PCR, Western blotting, and immunohistology. The results revealed that high d-glucose (25 mM) specifically stimulates UB branching morphogenesis via Pax-2 gene expression, whereas other glucose analogs, such as d-mannitol, l-glucose, and 2-deoxy-d-glucose, had no effect. The stimulatory effect of high glucose on UB branching was blocked in the presence of catalase and inhibitors of NADPH oxidase, mitochondrial electron transport chain complex I, and Akt signaling. Moreover, in in vivo studies, it seems that high glucose induces, via Pax-2 (mainly localized in UB), acceleration of UB branching but not nephron formation. Taken together, these data demonstrate that high glucose alters UB branching morphogenesis. This occurs, at least in part, via reactive oxygen species generation, activation of Akt signaling, and upregulation of Pax-2 gene expression.
Links	PubMed Online version:10.1681/ASN.2006101124
Keywords	Animals; Gene Expression; Glucose/pharmacology; Mice; Morphogenesis/drug effects; PAX2 Transcription Factor/genetics; Reactive Oxygen Species/pharmacology; Ureter/drug effects; Ureter/embryology
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:PAX2	involved_in	GO:0071333: cellular response to glucose stimulus	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PAX2	involved_in	GO:0070301: cellular response to hydrogen peroxide	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PAX2	involved_in	GO:0043491: protein kinase B signaling	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PAX2	involved_in	GO:0072593: reactive oxygen species metabolic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PAX2	involved_in	GO:0090190: positive regulation of branching involved in ureteric bud morphogenesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.