TRIP13-deficient tubular epithelial cells are susceptible to apoptosis following acute kidney injury

Jeffrey D. Pressly, Taketsugu Hama, Shannon O'Brien, Kevin R. Regner, Frank Park

Research output: Contribution to journalArticle

5 Citations (Scopus)

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/Gt hypomorph 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 (IH2AX) 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.

Original languageEnglish (US)
Article number43196
JournalScientific Reports
Volume7
DOIs
StatePublished - Mar 3 2017

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Receptor-Interacting Protein Serine-Threonine Kinases
Acute Kidney Injury
Thyroid Gland
Epithelial Cells
Apoptosis
Kidney
Reperfusion Injury
Caspase 7
In Situ Nick-End Labeling
Serine
Hydrogen Peroxide
DNA Damage
Cell Death

All Science Journal Classification (ASJC) codes

  • General

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TRIP13-deficient tubular epithelial cells are susceptible to apoptosis following acute kidney injury. / Pressly, Jeffrey D.; Hama, Taketsugu; O'Brien, Shannon; Regner, Kevin R.; Park, Frank.

In: Scientific Reports, Vol. 7, 43196, 03.03.2017.

Research output: Contribution to journalArticle

Pressly, Jeffrey D. ; Hama, Taketsugu ; O'Brien, Shannon ; Regner, Kevin R. ; Park, Frank. / TRIP13-deficient tubular epithelial cells are susceptible to apoptosis following acute kidney injury. In: Scientific Reports. 2017 ; Vol. 7.
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