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Abstract: TH-PO607

Defining the Renoprotective Mechanism of Deiodinase 3 in Podocytes

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1301 Health Maintenance, Nutrition, and Metabolism: Basic


  • Tardi, Nicholas J., Rush University Medical Center, Chicago, Illinois, United States
  • Dande, Ranadheer, Rush University Medical Center, Chicago, Illinois, United States
  • Reiser, Jochen, Rush University Medical Center, Chicago, Illinois, United States

Deiodinase 3 (D3) is a membrane-bound enzyme that reduces local thyroid hormone signaling in most cell types. By preventing the bioavailability of tri-iodothyronine (T3), the metabolically active thyroid hormone, D3 efficiently regulates thyroid signaling in tissues to modulate vital processes such as metabolism. While deiodinases have been studied in several endocrine tissues, the role of D3 in controlling T3 in renal tissue has not been addressed, despite emerging studies demonstrating overlapping complications of kidney disease and thyroid hormone dysfunction. As numerous glomerulopathies can stem from energetic dysfunction of podocytes, which have mechanisms that respond to both glomeruli derived and circulating changes in hormone levels, we aimed to determine the significance of D3 dysfunction in podocyte derived kidney disease.


D3 expression was measured via qRT-PCR, Western blot and confocal analysis. Regulatory capacity of D3 was analyzed via a T3 cleavage assay. The role of D3 in podocyte derived kidney disease was evaluated in vitro by inducing injury to cultured podocytes and in vivo using podocyte specific D3 KO mice challenged with LPS. Renal dysfunction was assessed by urine Albumin:Creatinine ratio and by quantifying effacement (processes/ GBM length). Cytoskeletal, metabolic and protein trafficking markers were measured in lentiviral-driven D3 knockdown podocytes to determine the renoprotective mechanism of D3. Glomerular D3 expression was measured in renal biopsies from kidney disease patients by immunofluorescence intensity.


D3 is highly expressed in podocytes and downregulated in injury models, resulting in compartmentalization of D3 in the golgi and nuclear region where metabolically active T3 resides. Podocyte specific D3 KO mice responded poorly to LPS-induced kidney injury, resulting in heavy proteinuria and foot process effacement compared to control. Biomarkers of metabolic stress and impaired protein trafficking were upregulated in D3 deficient podocytes. D3 expression in glomeruli of kidney disease patients suffering from minimal change disease, diabetic nephropathy, or focal segmental glomerulosclerosis showed unique profiles amongst diseases.


D3 plays a renoprotective role against thyroid hormone associated kidney disease in podocytes. We propose D3 reduces energy expenditure to prevent podocyte exhaustion and death.