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 X

Kidney Week

Please note that you are viewing an archived section from 2023 and some content may be unavailable. To unlock all content for 2023, please visit the archives.

Abstract: FR-PO1041

Protective Role of Tubular Interferon Regulatory Factor 5 (IRF5) Against Renal Tubulointerstitial Fibrosis

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms


  • Wu, Mengqiu, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
  • Jia, Zhanjun, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
  • Zhang, Aihua, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

Tubulointerstitial fibrosis (TIF) is the inevitable outcome of chronic kidney diseases, regardless of etiology. Interferon regulatory factor 5 (IRF5) is a key transcription factor involved in regulating the expression of proinflammatory cytokine and responses to infection in immune cells, but its role in renal epithelial cells and renal TIF remain unknown.


Renal biopsies of CKD patients and kidney of unilateral ureteral obstruction (UUO) and unilateral ischemia reperfusion (UIR) mice were used to evaluate the expression pattern of IRF5 in fibrotic kidneys. Then, the function of IRF5 was explored in UUO mice via high-throughput tail vein delivery of IRF5 over-expression plasmids or IRF5 targeting CRISPR/Cas9 plasmids. The TIF was histologically detected by Masson staining; pro-fibrosis gene expressions were evaluated via Western blotting and qRT-PCR techniques. In vitro, mouse proximal tubular epithelial cells (mPTCs) were transfected with IRF5 over-expression plasmids and then stimulated with TGF-β1 for phenotype evaluation. IRF5 over-expression mPTCs were also co-cultured with renal interstitial fibroblasts (NRK-49Fs) and macrophage cells (RAW 264.7). Finally, IRF5 overexpressing mPTCs were treated with Smad3 selective inhibitor SIS3 to explore whether the anti-fibrotic effect of IRF5 is Smad3 dependent.


IRF5 was consistently up-regulated in fibrotic kidneys of CKD patients and mice models, dominantly in the tubules. Overexpression of IRF5 markedly alleviated renal TIF, and knocking down of IRF5 significantly aggravated the degree of fibrosis in UUO mice. In vitro, overexpression of IRF5 inhibited TGF-β1 induced partial epithelial-mesenchymal transition (p-EMT) of mPTCs. IRF5 over-expression in TGF-β1 induced mPTCs also suppressed the activation of co-cultured NRK-49Fs and RAW 264.7 cells. Mechanic research revealed that IRF5 suppressed fibrotic response possibly by antagonizing TGF-β1/Smad3 signaling.


These findings demonstrated that up-regulation of IRF5 may inhibit p-EMT of tubular epithelial cells via antagonizing TGF-β1/Smad3 signaling. In turn, protected tubular epithelial cells attenuated the activation of interstitial fibroblasts and macrophages and thus attenuate kidney fibrosis. Targeted activation of IRF5 may serve as a potential intervention strategy in retarding CKD progression.


  • Government Support – Non-U.S.