title: TRIP13-deficient tubular epithelial cells are susceptible to apoptosis following acute kidney injury.
abstract: Damage to renal tubular epithelial cells by genetic, environmental, or biological insults can initiate complex signaling mechanisms that promote kidney repair and functional recovery. In this study, we demonstrated that thyroid receptor interacting protein 13 (TRIP13) is a critical modulator of tubular epithelial cell repair following ischemia-reperfusion injury (IRI), a common type of renal stressor. In Trip13Gt/Gthypomorph mice treated with unilateral renal IRI, persistent tubular epithelial cell damage was determined in the IRI-treated kidney throughout the 168 hours of experimental period compared to the contralateral kidneys. The damaged epithelial cells were associated with increased levels of DNA damage (ɣH2AX) and apoptotic markers (p53, cleaved caspase-7, and TUNEL-positive cells). Correspondingly, TRIP13 was found to directly interact with Tetratricopeptide Repeat Domain 5 (TTC5), a p53 co-factor, and genetic knockdown of TRIP13 in murine inner medullary collecting duct cells in the presence of hydrogen peroxide showed increased activity of p53 at Serine 15. In all, these studies suggest that insufficient TRIP13 increased the susceptibility of damaged tubular epithelial cells to progress towards apoptotic cell death.
authors.affiliation: The University of Tennessee Health Science Center, College of Pharmacy, Department of Pharmaceutical Sciences, Memphis, TN, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Pressly
authors.affiliation: The University of Tennessee Health Science Center, College of Pharmacy, Department of Pharmaceutical Sciences, Memphis, TN, USA.
authors.forename: Taketsugu
authors.initials: T
authors.lastname: Hama
authors.affiliation: The University of Tennessee Health Science Center, College of Pharmacy, Department of Pharmaceutical Sciences, Memphis, TN, USA.
authors.forename: Shannon O'
authors.initials: SO
authors.lastname: Brien
authors.affiliation: Medical College of Wisconsin, Department of Medicine, Division of Nephrology, Milwaukee, WI, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Regner
authors.affiliation: The University of Tennessee Health Science Center, College of Pharmacy, Department of Pharmaceutical Sciences, Memphis, TN, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Park
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities / Q000172:deficiency*; D058186:Acute Kidney Injury / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000172:deficiency*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology*; D051379:Mice; D011485:Protein Binding; D015427:Reperfusion Injury / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C000628667:Trp53 protein, mouse; C000629067:Ttc5 protein, mouse; D016159:Tumor Suppressor Protein p53; D000074183:ATPases Associated with Diverse Cellular Activities; C523791:Trip13 protein, mouse