GSE116760 RNA-Seq and protein mass spectrometry in microdissected kidney tubules reveal signaling processes initiating lithium-induced nephrogenic diabetes insipidus

Contributors : Chih_Chien Sung ; Lihe Chen ; Kavee Limbutara ; Hyun J Jung ; Gabrielle G Gilmer ; Chin-Rang Yang ; Shih-Hua Lin ; Sookkasem Khositseth ; Chung-Lin Chou ; Mark A KnepperSeries Type : Expression profiling by high throughput sequencingOrganism : Rattus norvegicusPurpose: Lithium salts, used for treatment of bipolar disorder, frequently induce nephrogenic diabetes insipidus (NDI), limiting therapeutic success. NDI is associated with loss of expression of the molecular water channel, aquaporin-2, in the renal collecting duct (CD). Here, we use the methods of systems biology in a well-established rat model of lithium-induced NDI to identify signaling pathways activated at the onset of polyuria.Methods: We carried out RNA-sequencing in cortical CDs microdissected from rats treated with lithium for 12-72 hours (vs. time controls). Administration of anti-inflammatory doses of dexamethasone to lithium-treated rats countered the loss of aquaporin-2 protein. Protein mass spectrometry in microdissected cortical CDs provided corroborative evidence, but also identified decreased abundance of several anti-oxidant proteins. Cortical thick ascending limbs of Henle were also microdissected for RNA-Seq at 72 hrs. We carried out RNA-Seq for 2-3 CCD sample per rat (1 lithium-treated rat versus 1 control at 12, 24, 36 hrs).Results and conclusion: Integration of new data with prior data about lithium effects at a molecular level leads to a signaling model in which lithium inc...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Rattus norvegicus Source Type: research