Loss of the Na

Autor: Adrienne, Bushau-Sprinkle, Michelle, Barati, Caryl, Conklin, Tess, Dupre, Kenneth B, Gagnon, Syed J, Khundmiri, Barbara, Clark, Leah, Siskind, Mark A, Doll, Madhavi, Rane, Michael, Brier, Susan, Coventry, Eleanor D, Lederer
Rok vydání: 2018
Předmět:
Zdroj: Am J Pathol
ISSN: 1525-2191
Popis: Na(+)/H(+) exchange regulatory cofactor (NHERF)-1, a scaffolding protein, anchors multiple membrane proteins in renal proximal tubules. Cultured proximal tubule cells deficient in Nherf1 and proximal tubules from Nherf1-deficient mice exhibit aberrant trafficking. Nherf1-deficient cells also exhibit an altered transcription pattern and worse survival. These observations suggest that NHERF1 loss increases susceptibility to acute kidney injury (AKI). Male and female wild-type C57BL/6J and Nherf1 knockout mice were treated with saline or cisplatin (20 mg/kg dose i.p.) to induce AKI and were euthanized after 72 hours. Blood and urine were collected for assessments of blood urea nitrogen and neutrophil gelatinase–associated lipocalin, respectively. Kidneys were harvested for histology (hematoxylin and eosin, periodic acid-Schiff) and terminal deoxynucleotidyl transferase dUTP nick end labeling assay, Kim1 mRNA assessment, and Western blot analysis for cleaved caspase 3. Cisplatin treatment was associated with significantly greater severity of AKI in knockout compared with wild-type mice, as demonstrated by semiquantitative injury score (2.8 versus 1.89, P
Databáze: OpenAIRE