Abstract

The present study investigated the effects of early bilateral ureteral obstruction (BUO)‐induced nephrogenic diabetes insipidus (NDI) on rat inner medullary collecting duct (IMCD). Immunoblotting of IMCD isolated from rats after 4 hours of BUO showed a 42% decrease in total Aqp2 (p <0.05), 65.5% decrease in pS256‐AQP2 (p <0.001), 34.4 % decrease in pS261‐AQP2 (p <0.01), but no significant change in total UT‐A1 and pS486‐UT‐A1 abundances. Large‐scale identification and quantification of BUO‐affected proteins in IMCD was performedby label‐free LC‐MS/MS technique. Of 1172 proteins identified, 52 proteins were found to have significant changes in abundance in early BUO rats versus sham controls, with 40 proteins increased and 12 proteins decreased. Gene Ontology terms and pathway analysis revealed that BUO‐affected proteins were associated with focal adhesion (Flnc, Actn4, Lamb2, Lama5, Lamc1, Col4a2, Ctnnb1), cytoskeleton (Krt7, Actn4, Myh10, Tubb4a, Cryab, Ctnnb1), and generation of precursor metabolites and energy (Atp6v1e1, Atp5h, Atp5a1, Atp5b, Aco2, Mdh1, Uqcrc2). Immunohistochemistry studies demonstrated aggregation of filamentous actin in IMCD of BUO rats. These results provide potential clues for understanding the mechanisms responsible for BUO‐induced NDI.Grant Funding Source: Supprted by Thailand Research Fund

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