GSE135868 Heme metabolism confronts urinary pathogens at the urothelium

Contributors : Katherine Xu ; Tian H Shen ; Atlas Khan ; Nicholas Tatonetti ; Krzysztof Kiryluk ; Jonathan BaraschSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe kidney and bladder expresses a variety of powerful defense mechanisms to limit urinary infection including iron scavenging, a process called "nutritional immunity". We previously demonstrated that bladder and kidney epithelia generates the archetype of the urinary iron defense, a lipocalin called NGAL which binds Enterochelin, a bacterial siderophore. However, because urinary bacteria can evade the bacteriostatic effects of NGAL by modifying Enterochelin and by producing additional siderophores, other mechanisms of "nutritional immunity" are anticipated. To study the defense in the kidney, we used a cell type specific method of RNA isolation in mouse (adapted from Gay et al, Oregon). A promiscuous form of phosphoribosyltransferase (UPRT) was cloned into the Rosa26 locus using a floxed-stop design which we activated in a cell specific fashion with Atp6v1b1-Cre. Thiouracil was introduced 12hr and 24hrs after urinary tract infection. Isolation of RNA directly from intercalated revealed synthetic (Npas1-Bmal1-Alas), transport (Hrg1, Flvcr1) and metabolic enzymes (Hmox1) of heme metabolism. Hmox1 was detected in the kidney with a luciferase based reporter (Contag et al, Stanford) after infection. CO production was detected in vivo and in AtpCre-mTmG FACS isolated intercalate...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research