Clinical and translational medicine · 2026
α7nAChR agonist GTS-21 ameliorates sepsis-induced acute kidney injury via MEF2/PGC-1α/HO-1 axis in mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Tang Yu-Jia, Liu Hui-Ying, Li Na-Qi, Zhang Xin, Lin Yi-Lu, Zhang Yan, Li Yao, Deng Jia-Le, Yang Pei-Lin, Meng Qing-Min, Tang Yi-Jin, Zhang Zi-Yue, Guan Si-Han, Kang Kai, Wang Hong-Liang, Gao Yang
Аннотация
BACKGROUND: Sepsis-induced acute kidney injury (S-AKI) is a major global public health concern, yet effective therapeutic strategies remain limited. Mitochondrial dysfunction in renal tissues is a key pathogenic mechanism underlying S-AKI. GTS-21, a selective α7 nicotinic acetylcholine receptor (α7nAChR) agonist, exhibits anti-inflammatory and renoprotective effects in S-AKI.
METHODS: We investigated the role of α7nAChR in S-AKI using both in vitro (lipopolysaccharide (LPS)-induced renal tubular cell injury) and in vivo (caecal ligation and puncture (CLP)-induced septic mice) models, with GTS-21 treatment.
RESULTS: GTS-21 significantly attenuated mitochondrial dysfunction, suppressed apoptosis, and alleviated inflammation, thereby protecting renal tubular cells and renal tissues against LPS- and CLP-induced injury. Mechanistically, GTS-21 activated α7nAChR and upregulated myocyte enhancer factor 2 (MEF2), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and heme oxygenase-1 (HO-1), which collectively mediate its anti-oxidative, anti-apoptotic and anti-inflammatory effects.
CONCLUSION: These findings suggest that GTS-21 may represent a potential therapeutic strategy for sepsis-induced kidney injury.
METHODS: We investigated the role of α7nAChR in S-AKI using both in vitro (lipopolysaccharide (LPS)-induced renal tubular cell injury) and in vivo (caecal ligation and puncture (CLP)-induced septic mice) models, with GTS-21 treatment.
RESULTS: GTS-21 significantly attenuated mitochondrial dysfunction, suppressed apoptosis, and alleviated inflammation, thereby protecting renal tubular cells and renal tissues against LPS- and CLP-induced injury. Mechanistically, GTS-21 activated α7nAChR and upregulated myocyte enhancer factor 2 (MEF2), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and heme oxygenase-1 (HO-1), which collectively mediate its anti-oxidative, anti-apoptotic and anti-inflammatory effects.
CONCLUSION: These findings suggest that GTS-21 may represent a potential therapeutic strategy for sepsis-induced kidney injury.