Abstract: TH-PO0228
Activated Interstitial Cells May Contribute to NBL1 Induction in Kidney Injury via TGF-β-Smad Signaling
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 1
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Kobayashi, Hiroki, Nihon Daigaku Igakubu Daigakuin Igaku Kenkyuka, Itabashi, Tokyo, Japan
- Abe, Masanori, Nihon Daigaku Igakubu Daigakuin Igaku Kenkyuka, Itabashi, Tokyo, Japan
Background
Elevated circulating NBL1 levels are associated with increased risk of end-stage kidney disease in diabetes. We previously showed that NBL1 deficiency attenuates experimental kidney injury, but the cellular context of NBL1 induction remains unclear. This study examined the link between TGF-β/Smad activation, epithelial injury responses, and NBL1 induction.
Methods
HK-2 cells were treated with recombinant NBL1 for 72 hours, and epithelial–mesenchymal transition-related markers were assessed. NBL1 knockout mice and wild-type littermates were subjected to cisplatin-induced acute kidney injury or unilateral ureteral obstruction-induced chronic kidney injury. Kidney function, gene/protein expression, histology, apoptosis, and immunohistochemistry were analyzed. Cultured renal fibroblasts were stimulated with TGF-β1 to evaluate αSMA and NBL1 expression.
Results
In HK-2 cells, NBL1 increased TGF-β1, αSMA, fibronectin, and vimentin expression, reduced E-cadherin protein expression, and enhanced Smad2/3 phosphorylation. In the cisplatin model, renal NBL1 expression increased in wild-type mice after injury. NBL1 knockout mice showed less severe renal dysfunction, lower expression of TGF-β1, αSMA, fibronectin, and MCP-1, preserved E-cadherin expression, reduced Smad2/3 phosphorylation, fewer apoptotic cells, and reduced Mac-1-positive inflammatory cell infiltration. PAS-based injury scores did not significantly differ.
In the unilateral ureteral obstruction model, renal NBL1 mRNA and serum NBL1 protein increased in wild-type mice. NBL1 knockout mice showed lower expression of TGF-β1, CTGF, αSMA, fibronectin, collagen 4a1, and vimentin, with preserved E-cadherin expression and suppressed Smad2/3 phosphorylation. Histological injury scores were not significantly different. Wild-type mice showed prominent interstitial αSMA staining. In cultured renal fibroblasts, TGF-β1 induced αSMA and NBL1 expression, suggesting that activated interstitial cells may contribute to NBL1 induction during kidney injury.
Conclusion
NBL1 promotes epithelial injury responses, inflammation, and fibrotic signaling through TGF-β/Smad activation. TGF-β1-induced renal interstitial cell activation may contribute to NBL1 induction, potentially forming a feed-forward mechanism that amplifies kidney injury and fibrosis. NBL1 may represent a novel therapeutic target.