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Abstract: SA-PO566

Inhibition of Human Antigen R Reduces Glomerular Injury in Experimental Glomerulonephritis

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix


  • Liu, Simeng, University of Utah School of Medicine, Salt Lake City, Utah, United States
  • Huang, Zhimin, University of Utah School of Medicine, Salt Lake City, Utah, United States
  • Huang, Yufeng, University of Utah School of Medicine, Salt Lake City, Utah, United States

Group or Team Name

  • Internal Medicine, Div. of Nephrology, University of Utah

Recent identification of a mRNA-binding protein (human antigen R (HuR)) that regulates mRNA turnover and translation of numerous genes involved in immune response, inflammation, fibrosis and oncogenic signaling and is abnormally elevated in varied kidney diseases offers a novel target for the treatment of renal fibrosis. Thus, we hypothesized that therapy with a selective inhibition of HuR function with a small molecule, KH3, would reduce inflammation and profibrotic factors thereby improving glomerulosclerosis in experimental glomerulonephritis.


Three experimental groups included normal, untreated disease control, and KH3-treated nephritic rats. Disease was induced in rats with monoclonal anti-thy 1.1 antibody. KH3 was given via daily intraperitoneal injection from day 1 after disease induction at the dose of 50mg/kg BW/day.


At day 6, animals treated with KH3 showed significant reductions in proteinuria, podocyte injury determined by ameliorated podocyte loss and glomerular podocin expression, glomerular staining for periodic acid-Schiff positive material (41%), fibronectin (52%) and collagen IV (48%) and in collagen and fibronectin mRNA levels and protein production. Treatment with KH3 also reduced disease-induced increases in renal TGF-ß1 and PAI-1 mRNA levels and protein levels. Additionally, a marked increase in renal production of NF-kb-p65 and Nox4 and glomerular macrophage cell infiltration observed in disease control group was largely reversed by treatment with KH3.


These observations strongly support our hypothesis that inhibition of HuR with KH3 has therapeutic potential for reversing glomerulosclerosis by inhibiting inflammatory cell infiltration, decreasing local NAPDH oxidase-mediated oxidative stress, and TGFß and PAI-1’s expression and action.