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Abstract: SA-OR090

Role of Cyclin G1 in Maladaptive Repair and Kidney Fibrosis

Session Information

Category: Acute Kidney Injury

  • 002 AKI: Repair and Regeneration


  • Scott, Adam W, Boston Children's Hospital, Boston, Massachusetts, United States
  • Brooks, Craig R., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Ichimura, Takaharu, Brigham & Women's Hospital/Harvard Medical School, Boston, Massachusetts, United States
  • Bonventre, Joseph V., Brigham & Women's Hospital/Harvard Medical School, Boston, Massachusetts, United States

Survivors of acute kidney injury (AKI) have an increased risk for the development of chronic kidney disease (CKD). Previous work from our lab has demonstrated that G2/M cell cycle arrest is an important driver for the maladaptive repair process that leads to renal fibrosis. Using unbiased gene expression profiling, one of the major pathways upregulated following injury is the p53 pathway, and within this pathway cyclin G1 expression was increased. While the exact function of cyclin G1 is not well known, it is known to interact with p53 and is involved in cell cycle arrest at G2/M. We hypothesize that cyclin G1 plays a critical role in the maladaptive repair process following AKI that leads to progressive fibrosis and CKD.


We transfected HK-2 cells with the mouse (mCG1) or human form of cyclin G1 (hCG1), and analyzed cell cycle markers as well as inflammatory cytokines. Using a global knockout murine model of cyclin G1 compared with wild-type mice, we performed bilateral IRI to evaluate the effect of cyclin G1 on AKI. Animals were sacrificed at 48 hours and 7 days. We then analyzed markers of renal dysfunction and routine histology. We also performed immunofluorescence experiments staining for KIM-1 to compare proximal tubule injury between the two groups.


Transfection with either mCG1 or hCG1 in vitro induced a higher percentage of cells into G2/M phase. These cells also demonstrated increased production of TGF-beta and CTGF. At 48 hours after ischemic kidney injury, there was a tendency towards increased KIM-1 staining by immunofluorescence in the wild-type animals compared to cyclin G1 knockout animals. At 7 days, KIM-1 staining by immunofluorescence was decreased in the knockout animals compared to wild-type mice. Histologically, there was a decreased amount of tubular injury, including reduced inflammatory response and tubular vacuolization, in the knockout animals compared to the wild-type animals.


Cyclin G1 overexpression leads to an increase in the number of cells in the G2/M phase of the cell cycle, and is associated with a pro-inflammatory phenotype. In vivo, cyclin G1 is associated with a more severe injury phenotype in an animal model of AKI. In vivo knockout of cyclin G1 expression led to decreased proximal tubular injury and suggests a role for cyclin G1 in promoting maladaptive repair following AKI that leads to renal fibrosis.


  • NIDDK Support