Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models

Qingqing Wei, Guie Dong, Jian Kang Chen, Ganesan Ramesh, Zheng Dong

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56 Citations (Scopus)

Abstract

Bax and Bak, two pro-apoptotic Bcl-2 family proteins, have been implicated in acute kidney injury following renal ischemia/reperfusion; however, definitive evidence for a role of these genes in the disease process is lacking. Here we first examined two Bax-deficient mouse models and found that only conditional Bax deletion specifically from proximal tubules could ameliorate ischemic acute kidney injury. Global (whole mouse) knockout of Bax enhanced neutrophil infiltration without significant effect on kidney injury. In contrast, global knockout of Bak protected mice from ischemic acute kidney injury with improved renal function. Interestingly, in these models, Bax or Bak knockout attenuated renal tubular cell apoptosis without significantly affecting necrotic tubular damage. Cytochrome c release in ischemic acute kidney injury was also suppressed in conditional Bax- or global Bak-knockout mice. In addition, Bak deficiency prevented mitochondrial fragmentation in ischemic acute kidney injury. Thus, our gene-knockout studies support a critical role of Bax and Bak in tubular cell apoptosis in ischemic acute kidney. Furthermore, necrosis and apoptosis have distinguishable regulatory functions.

Original languageEnglish (US)
Pages (from-to)138-148
Number of pages11
JournalKidney International
Volume84
Issue number1
DOIs
StatePublished - Jul 2013

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Acute Kidney Injury
Knockout Mice
Kidney
Apoptosis
Gene Knockout Techniques
Neutrophil Infiltration
Cytochromes c
Reperfusion
Necrosis
Ischemia
Wounds and Injuries
Genes
Proteins

ASJC Scopus subject areas

  • Nephrology

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Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models. / Wei, Qingqing; Dong, Guie; Chen, Jian Kang; Ramesh, Ganesan; Dong, Zheng.

In: Kidney International, Vol. 84, No. 1, 07.2013, p. 138-148.

Research output: Contribution to journalArticle

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