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Abstract: TH-PO765

Loss of PRDM16 Aggravated Podocytopathies by Regulating Insulin Signaling

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology


  • Yuan, Qian, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • Tang, Ben, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • Zhang, Chun, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Podocytopathies are kidney diseases that are characterized by proteinuria or nephrotic syndrome due to direct or indirect podocyte injury. Our lab has investigated the effect of tubular PRDM16 on renal fibrosis. And we found that the expression of PRDM16 was abundant in healthy podocytes, however, decreased greatly in injured podocytes. In this study, we aim to clarify the function of PRDM16 on podocyte injury.


The expression of PRDM16 in the podocytes of podocytopathies patients and mice was detected by Western Blot, qPCR and Co-immunofluorescence staining . Podocyte-specific PRDM16 knockout mice were generated, and Streptozotocin-induced diabetic nephrology (DN) model was established. Kidneys, urine, and blood were collected. Lentivirus was used to overexpress PRDM16 in podocytes, and FSGS and DN animal models. Western Blot, qPCR, IHC, IF, electron microscope, urinary albumin to creatine ratio (ACR), Masson’s staining, and PAS staining were used to verify the podocytes-protected role of PRDM16 in vivo and in vitro. RNA-sequencing, glucose intake assay, glycolysis detecting with seahorse bioanalyzer, ChIP, Co-IP, and luciferase assay were used to clarify the mechanism of PRDM16 on insulin signaling.


The results showed PRDM16 was decreased markedly in the podocytes of Podocytopathies patients and mice. Renal injection with PRDM16 overexpression lentivirus decreased proteinuria and podocyte injury of Adriamycin nephropathy and DN mice. Podocyte-specific PRDM16 knockout diabetic mice showed more severe proteinuria and podocyte injury compared to PRDM16fl/fl diabetic mice. RNA-sequencing results revealed that insulin signaling changed obviously in PRDM16 overexpression podocytes. And we verified that PRDM16 promoted the transduction of insulin signaling and glucose metabolism by inhibiting the Ser307 phosphorylation of insulin receptor substrate-1(IRS-1) which was recognized and degraded by the ubiquitin-proteasome system. The mechanism of PRDM16 regulating the phosphorylation of IRS-1 was inhibiting the transcription of serine-threonine kinase, IKK-β.


Loss of PRDM16 in podocytes aggravated podocyte injury by inhibiting insulin signaling and successive glucose metabolism. Mechanistically, PRDM16 blocked the Ser307 phosphorylation of IRS-1 by downregulating the transcription of IKK-β.


  • Government Support – Non-U.S.