C/EBP homologous protein (CHOP) gene deficiency attenuates renal ischemia/reperfusion injury in mice.
- Alternative Author(s)
- Kim, Jee In
- Publication Year
- C/EBP homologous protein; CHOP; ER stress; Ischemia; Apoptosis
- C/EBP homologous protein (CHOP), a transcription factor for the expression of apoptosis-related genes, plays an
important role in endoplasmic reticulum (ER) stress-related organ diseases, including diseases of the kidney.
Here, we investigated the role of CHOP in ischemia/reperfusion (I/R)-induced acute kidney injury using
CHOP-knockout (CHOP−/−) and wild type (CHOP+/+) mice. Fifteen or thirtyminutes of bilateral renal ischemia
(I/R) insult resulted in necrotic and apoptotic tubular epithelial cell death, together with increases in plasma
creatinine (PCr) and blood urea nitrogen (BUN) concentrations. After I/R, BiP/GRP78 and CHOP expressions in
the kidney gradually increased over time. CHOP expression was greater in the outer medulla than that in the
cortex and localized intensely in the nucleus. I/R caused apoptosis of tubular epithelial cells in both CHOP−/−
and CHOP+/+ mice. The number of apoptotic cells after I/R was lower in CHOP−/− mice than that in CHOP+/+
mice. Consistent with the degree of apoptosis, I/R-induced kidney morphological and functional damages were
milder in CHOP−/− than that in CHOP+/+ mice. The cleavage of procaspase-3 and the induction of Bax protein
after I/R were lower in CHOP−/− than that in CHOP+/+ mice. In contrast, the expression levels of Bcl-2, Bcl-xL,
cIAP2, Mcl-1, and XIAP were higher in CHOP−/− than that in CHOP+/+ mice. These results indicate that I/R
induces ER stress, leading to the activation of CHOP-associated apoptosis signals, resulting in renal functional
and histological damages.
- Authorize & License
- Files in This Item:
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.