ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

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
  • 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
  • Gupta, Vineet, 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