Abstract: TH-PO0297
Astragaloside IV Restores ARNTL-Mediated Circadian Control of NF-κB Signaling to Attenuate Tubular Inflammation in CKD
Session Information
- Glomerular Diseases: Cell Biology
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Author
- He, Li, Shanghai 6th Peoples Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China
Background
Circadian clock disruption is increasingly recognized as a contributor to chronic kidney disease (CKD); however, the mechanisms linking circadian dysregulation to tubular inflammation remain poorly defined. Through transcriptomic analyses, ARNTL (BMAL1) was identified as a key downregulated hub regulator in CKD. We investigated whether loss of ARNTL drives inflammatory amplification through NF-κB signaling and whether Astragaloside IV (AS-IV) exerts renoprotective effects through pharmacologic restoration of ARNTL signaling.
Methods
Adenine-induced CKD mice and adenine-treated HK-2 cells were used to evaluate tubular injury. ARNTL expression and NF-κB signaling were assessed by qPCR, western blotting, and immunohistochemistry. Gain- and loss-of-function studies were performed to determine the mechanistic role of ARNTL in inflammatory signaling and mitochondrial apoptosis. Protein interaction and transcriptional regulatory analyses were conducted to examine the relationship between ARNTL and NF-κB/p65. AS-IV was administered in vivo and in vitro to evaluate its effects on ARNTL signaling and renal injury.
Results
ARNTL was significantly downregulated in CKD and positively correlated with renal function. Reduced ARNTL in CKD kidneys and adenine-treated HK-2 cells was accompanied by NF-κB activation, increased inflammatory cytokines, and mitochondrial injury. ARNTL deficiency promoted p65 nuclear translocation, enhanced NF-κB transcriptional activity, and aggravated mitochondrial apoptosis in tubular cells, whereas ARNTL restoration suppressed p65 activation and inflammatory amplification. Mechanistically, ARNTL directly interacted with p65 and repressed NF-κB–dependent inflammatory transcription. AS-IV restored ARNTL expression, inhibited p65 activation, reduced IL-1β expression, and attenuated tubular injury in CKD mice and HK-2 cells. ARNTL silencing largely abolished the anti-inflammatory and anti-apoptotic effects of AS-IV, indicating that ARNTL is required for AS-IV-mediated renoprotection.
Conclusion
ARNTL acts as a molecular brake linking circadian clock disruption to NF-κB–driven tubular inflammation in CKD. AS-IV restores ARNTL signaling, reducing inflammation and mitochondrial apoptosis. These findings identify an ARNTL-centered circadian-inflammatory axis as a potential therapeutic target for CKD.
Funding
- NIDDK Support