TRIP13-deficient tubular epithelial cells are susceptible to apoptosis following acute kidney injury. Sci Rep 2017 Mar 03;7:43196
Date
03/04/2017Pubmed ID
28256593Pubmed Central ID
PMC5335694DOI
10.1038/srep43196Scopus ID
2-s2.0-85014629995 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
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.
Author List
Pressly JD, Hama T, Brien SO, Regner KR, Park FAuthor
Kevin R. Regner MD Interim Chair, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ATPases Associated with Diverse Cellular ActivitiesAcute Kidney Injury
Animals
Apoptosis
Cell Cycle Proteins
DNA-Binding Proteins
Epithelial Cells
Mice
Protein Binding
Reperfusion Injury
Transcription Factors
Tumor Suppressor Protein p53
