Abstract: TH-PO0217
Activation of α7 Nicotinic Acetylcholine Receptor in Fibroblasts Suppresses Renal Fibrosis via HO-1-Mediated Redox Regulation
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
- Furumoto, Sakika, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
- Shimoyama, Kotaro, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
- Umene, Ryusuke, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
- Wu, Chia-Hsien, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
- Nakamura, Yasuna, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
- Inoue, Tsuyoshi, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
Background
Progressive renal fibrosis is a hallmark of Chronic Kidney Disease (CKD) and contributes to the decline of renal function. Although cholinergic stimulation has been reported to suppress CKD progression, the mechanisms underlying its anti-fibrotic effects within the kidney remain poorly understood. The α7 nicotinic acetylcholine receptor (α7nAChR) has been reported to exert anti-inflammatory and tissue-protective effects in various organs. In the kidney, we found that α7nAChR is highly expressed in fibroblasts by single-cell RNA sequencing; however, its role in renal fibrosis remains unclear. Therefore, this study investigated the effects of α7nAChR agonists on renal fibrosis using both in vivo and in vitro models.
Methods
Using a unilateral ureteral obstruction (UUO) mouse model, renal fibrosis was evaluated following treatment with daily nicotine(1 mg/kg) i.p.or the selectiveα7nAChR agonist GTS-21(20 mg/kg) i.p.. Fibrosis was assessed by histological staining and qPCR analysis of fibrosis-related genes. In vitro, NIH3T3 fibroblasts were stimulated with TGFβ in the presence or absence of nicotine or GTS-21 to evaluate fibroblast activation. RNA sequencing was performed to identify downstream mediators.
Results
Nicotine and the selectiveα7nAChR agonist GTS-21 attenuated renal fibrosis in the UUO model, as demonstrated by reduced expression of fibrosis-related genes. In NIH3T3 fibroblasts, nicotine and GTS-21 suppressed TGFβ-induced αSMA expression. RNA sequencing revealed activation of oxidative stress response pathways, including marked upregulation of Hmox1, which encodes heme oxygenase-1 (HO-1), a molecule reported to exert anti-fibrotic effects by suppressing reactive oxygen species (ROS). Administration of recombinant HO-1 suppressed TGFβ-induced αSMA expression and reduced intracellular ROS levels.
Conclusion
Stimulation of α7 nicotinic acetylcholine receptor (α7nAChR) attenuates fibrosis through suppression of oxidative stress via HO-1 induction. These findings identify α7nAChR-mediated signaling as a potential therapeutic pathway for chronic kidney disease–associated fibrosis.
Funding
- Government Support – Non-U.S.