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Abstract: FR-PO347

Hic-5 Overexpression Drives Tubular Cell Senescence and Degeneration in Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic


  • Chen, Bohan, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
  • Liang, Xianhui, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
  • Wang, Pei, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

Emerging data suggest that tubular cell senescence plays a crucial role in the onset and development of diabetic kidney disease (DKD). However, the underlying mechanism responsible for the tubular cell senescence of DKD remains elusive. Hydrogen peroxide-induced clone 5 (Hic-5) has been shown to be associated with senescence-related genes and cell-senescent phenotypes. Ergo, this study investigated the role of Hic-5 in DKD tubular cell senescence.


The expression of Hic-5 was examined in kidney tissues of DKD patients. The effect of Hic-5 was explored in vitro in cultured tubular epithelial cells by knockdown or by forced expression of Hic-5 in diabetic milieu, or in vivo in mouse models of DKD with knockdown of Hic-5. The cell senescent phenotype, tubular degeneration or kidney injury as well as function were tested.


The tubulointerstitial expression of Hic-5 was markedly increased in kidney tissues of DKD patients, as compared with healthy living donors, which was positively associated with the curated kidney-aging-related gene set “RODWELL_AGING_KIDNEY_UP”, as analyzed by gene set enrichment analysis. In vitro in cultured tubular epithelial cells exposed to diabetic milieu, Hic-5 was significantly increased accompanied by increased expression of p16INK4A, fibronectin, and increased cell senescence-associated beta-galactosidase activity as well as reduced expression of the epithelial marker E-cadherin. All these senescent phenotypes and degenerative changes were largely abrogated by knockdown of Hic-5 but reinforced by forced expression of Hic-5. In vivo in mouse models of DKD, knockdown of tubular Hic-5 expression mitigated tubular cell senescence and secretion of senescence-associated secretory phenotype including IL6, monocyte chemoattractant protein 1 and plasminogen activator inhibitor 1, concomitant with attenuated kidney function as well as decreased fibronectin and collagen I expression of the kidney.


Hic-5 plays an instrumental role in DKD progression by mediating cellular senescence, and thus is likely a drugable target for halting DKD progression.