#WTC2014: Inducible Knockdown of SHROOM3 Reduces Renal Fibrosis in Mice: From Bedside to Bench

In the last plenary session of the day, Dr. Madhav Menon from Mt. Sinai, NY, presented an interesting study that really exemplifies translational research. The story of the study begins with findings extrapolated from the GoCAR (Genomics of Chronic Allograft Rejection) study. The GoCAR study was an international multicenter study where prospectively enrolled patients had blood samples and protocol kidney transplant biopsies collected at the time of implantation, 3 mo, 12 mo, and 24 mo post transplantation. Blood and tissue were used for histology and genomics. Analysis of the study data revealed a polymorphism in SHROOM3 as a predictor for poor 12 month post-transplant GFR and fibroses. Interestingly the same polymorphism (rs17319721) had been found to be associated with CKD in genome-wide association studies. The risk allele was found to increase SHROOM3 expression. As the next step in investigation this relationship the authors went back to the “bench” to investigate if SHROOM3 expression correlates with fibroses in a murine model. To test their hypothesis they developed a SHROOM3 knockdown murine model. They performed unilateral ureteral obstruction (UUO) in the knockdown mice and control mice then sacrificed them 10 days after. As expected there was higher expression of SHROOM3 in the UUO kidneys than the control kidneys. However, in the UUO kidneys collagen 1 and fibronectin 1 transcripts were significantly inhibited in the SHROOM3 knockdown animals compared to controls. Interstitial fibroses was also significantly reduced in the knockdown mice with UUO. The same association was found with type 4 collagen staining. The authors concluded that SHROOM3 facilitates fibrotic factors and knockdown of SHROOM3 ameliorates renal fibroses. If this hold true SHROOM3 may be a therapeutic target in chronic allograft nephropathy and even CKD. Hopefully more to come about this in the future.

Post written by Dr. Vinay Nair, eAJKD Advisory Board member.

Check out more of eAJKD’s coverage of the 2014 World Transplant Congress here and on Twitter (@eAJKD)!

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