Specific deletion of glycogen synthase kinase-3β in the renal proximal tubule protects against acute nephrotoxic injury in mice

Renal proximal tubular damage and repair are hallmarks of acute kidney injury. Because glycogen synthase kinase-3β (GSK-3β) is an important cellular regulator of survival and proliferation, we determined its role during injury and recovery of proximal tubules in a mercuric chloride-induced nephrotoxic model of acute kidney injury. Renal proximal tubule-specific GSK-3β knockout mice exposed to mercuric chloride had improved survival and renal function compared to wild type mice. Apoptosis, measured by TUNEL staining, Bax activation, and caspase 3 cleavage were all reduced in the knockout mice. The restoration of renal structure, function, and cell proliferation was also accelerated in the GSK-3β knockout mice. This enhanced repair, evidenced by increased Ki-67 and BrdU staining, along with increased cyclin D1 and c-myc levels, was recapitulated by treatment of wild type mice with the small-molecule GSK-3 inhibitor TDZD-8 following injury. This confirmed that hastened repair in the knockout mice was not merely due to lower initial injury levels. Thus, inhibition of GSK-3β prior to nephrotoxic insult protects from renal injury. Such treatment after acute kidney injury may accelerate repair and regeneration.

• Publication year

  2012

• Venue

  Kidney International

• Publication date

  2012-06-04

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/ki.2012.239PMID 22785175PMCID 3472082
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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