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The Changing Phenotype of Tubular Cell Death during Delayed Graft Function


Jain, Swati; Galešić Ljubanović, Danica; Edelstein, Charles L.; Jani, Alkesh
The Changing Phenotype of Tubular Cell Death during Delayed Graft Function // J Am Soc Nephrol
Philadelphia, SAD, 2014. (poster, međunarodna recenzija, sažetak, znanstveni)


Naslov
The Changing Phenotype of Tubular Cell Death during Delayed Graft Function

Autori
Jain, Swati ; Galešić Ljubanović, Danica ; Edelstein, Charles L. ; Jani, Alkesh

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
J Am Soc Nephrol / - , 2014

Skup
ASN Kidney Week 2014

Mjesto i datum
Philadelphia, SAD, 11-16.11.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Tubular Cell Death; Delayed Graft Function

Sažetak
Background: Delayed graft function (DGF) independently predicts reduced 5 yr kidney transplant survival. Treatments of DGF are lacking. Cold ischemia (CI) is a significant risk factor for DGF but the mechanism by which CI leads to DGF is unknown. The effect of CI alone versus CI + warm reperfusion (WR) on renal tubular cell (RTEC) death are not well defined. The aim of this study was to determine the relative effects of CI vs CI+WR on donor kidneys in a kidney transplant model of DGF. We hypothesized that CI alone would produce a different injury phenotype to CI+WR. Methods: Male C57BL6 mice aged 12 weeks were subjected to mouse kidney transplant. Donor kidneys subjected to 3 hours CI at 4°C in UW solution, were either processed immediately or subjected to syngeneic mouse kidney transplant. Renal function was assessed by serum creatinine (SCr). RTEC apoptosis and necrosis were assessed by a nephropathologist in a blinded fashion. Results: CI alone significantly increased RTEC apoptosis but did not result in necrosis. In contrast, CI+WR after transplant caused RTEC apoptosis and necrosis. SCr was significantly increased in transplants subjected to CI vs. no CI. Since caspase-8 is known to trigger apoptosis and also serves as a negative regulator of programmed necrosis, we examined caspase-8 protein expression and activity. Caspase-8 activity and protein expression were significantly decreased in CI+WR vs CI alone.Conclusions: We have shown that CI alone results in RTEC apoptosis whereas CI+WR after mouse kidney transplant results in a different injury phenotype with the development of RTEC necrosis. A potential mechanism by which these differing phenotypes may occur is via decreased caspase-8 after CI+WR, thus removing negative regulation of programmed necrosis. These studies suggest that while inhibition of capsase- 8 may prevent RTEC apoptosis, a consequence might be increased RTEC necrosis.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti



POVEZANOST RADA


Projekt / tema
198-0000000-3355 - Značaj morfoloških čimbenika u dijagnostici, terapiji i prognozi FSGS (Danica Galešić-Ljubanović, )

Ustanove
Medicinski fakultet, Zagreb,
Klinička bolnica "Dubrava"

Autor s matičnim brojem:
Danica Galešić-Ljubanović, (203674)

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE