Abstract: SA-PO217

Podocyte Expressed miR-146a Protects against Diabetic Glomerulopathy via Suppression of ErbB4 and Notch-1

Session Information

  • Glomerular: Cell Biology
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Glomerular

  • 1003 Glomerular: Cell Biology


  • Geraghty, Terese D., Rush University, Chicago, Illinois, United States
  • Gupta, Vineet, Rush University Medical Center, Chicago, Illinois, United States
  • Khan, Samia, None, Chicago, Illinois, United States
  • Khaliqdina, Shehryar J., Rush University Medical Center, Chicago, Illinois, United States
  • Lee, Ha Won, Rush University Medical Center, Chicago, Illinois, United States
  • Altintas, Mehmet M., Rush University, Chicago, Illinois, United States
  • Tharaux, Pierre-Louis, INSERM, Paris, France
  • Huber, Tobias B., University Medical Center Hamburg, Hamburg, Germany
  • Bitzer, Markus, University of Michigan, Ann Arbor, Michigan, United States
  • Reiser, Jochen, Rush University Medical Center, Chicago, Illinois, United States

Diabetic glomerulopathy is a major complication of Diabetes Mellitus (DM) and is the leading cause of end stage renal disease (ESRD). MicroRNA-146a (miR-146a) is a negative regulator of inflammation and is highly expressed in myeloid cells and in podocytes. We have previously shown that miR-146a levels are significantly reduced in the glomeruli of diabetic nephropathy (DN) patients. To study its role in podocyte function, we have generated mice with selective deletion of miR-146a in podocytes. Here we will present our results from studies in these animals.


We generated and characterized podocyte-specific miR-146a deficient mice. To investigate the role of miR-146a in glomerular function in vivo, we induced hyperglycemia in C57BL/6 wildtype mice (WT), global miR-146a knockout mice (miR-146a-/-) and podocyte-specific miR-146a knockout (KO) animals using streptozotocin (STZ).


We further confirmed that podocytic miR-146a expression decreased in the glomeruli of type 2 diabetes (T2D) patients and correlated with increased albuminuria and glomerular damage. Mice lacking miR-146a globally or selectively in podocytes showed accelerated development of glomerulopathy upon STZ-induced hyperglycemia. miR-146a targets, Notch-1 and ErbB4, were significantly upregulated in the diseased glomeruli and TGFβ signaling was induced. Treatment of podocytes in vitro with TGFβ resulted in increased levels of Notch-1 and ErbB4, increased ErbB4 phosphorylation, and increased expression of inflammatory chemokine MCP-1, which suppresses miR-146a via an autocrine loop. Similarly, administration of low-dose LPS to podocyte-specific miR-146a KO mice resulted in increased albuminuria as compared to the WT mice, further suggesting that podocyte-expressed miR-146a protects from glomerular damage.


We suggest a novel role for miR-146a in protecting against glomerular injury via protecting podocytes from injury and cell death. This indicates that miR-146a might have a therapeutic potential in DN.


  • NIDDK Support