Chen Kuan-Hsing, Hsu Hsiang-Hao, Yang Huang-Yu, Ko Yi-Ching, Hung Cheng-Chieh
Kidney Research Center, Chang Gung Memorial Hospital, Chang Gung University, School of Medicine, Taoyuan, Taiwan; Center for Healthy and Aging Research, Chang Gung University, Taoyuan, Taiwan.
Kidney Research Center, Chang Gung Memorial Hospital, Chang Gung University, School of Medicine, Taoyuan, Taiwan.
Biochem Biophys Res Commun. 2025 Jan;742:151130. doi: 10.1016/j.bbrc.2024.151130. Epub 2024 Dec 6.
Renal fibrosis is a crucial pathological feature in chronic kidney disease (CKD), resulting in the gradual decline of renal function. Salinomycin is an antibiotic discovered from Streptomyces albus that also regulates the fates of cells. However, its potential in kidney fibrosis remains elusive. In this study, salinomycin was administrated to a renal fibrosis mouse model with unilateral ureteral obstruction (UUO) and a kidney fibroblast cell line (NRK-49F cells) treated with transforming growth factor-β1 (TGF-β1). In vivo, salinomycin treatment attenuated tubulointerstitial fibrosis, as evidenced by Gomori's trichrome staining, in line with decreased mRNA and protein expressions of fibronectin, collagen type I/IV, in the UUO kidneys. Furthermore, inflammasome mRNA level in the kidney with UUO was also suppressed by salinomycin. In vitro, salinomycin administration impeded the upregulation of fibronectin, collagen type I/IV, and ⍺-smooth muscle actin in NRK-49F cells stimulated with TGF-β1. Importantly, the inhibitory properties of salinomycin were correlated with reduction of Smad2/3 and MAPK-p38 phosphorylation. Together, our data indicate salinomycin as a potential medication to counteract renal fibrosis in patients with CKD.
肾纤维化是慢性肾脏病（CKD）的关键病理特征，会导致肾功能逐渐下降。盐霉素是从白色链霉菌中发现的一种抗生素，它也能调节细胞命运。然而，其在肾纤维化方面的潜力仍不明确。在本研究中，将盐霉素应用于单侧输尿管梗阻（UUO）诱导的肾纤维化小鼠模型，并对用转化生长因子-β1（TGF-β1）处理的肾成纤维细胞系（NRK-49F细胞）进行实验。在体内，盐霉素治疗减轻了肾小管间质纤维化，如Gomori三色染色所示，同时UUO肾脏中纤连蛋白、I/IV型胶原的mRNA和蛋白表达降低。此外，盐霉素还抑制了UUO肾脏中炎性小体的mRNA水平。在体外，盐霉素给药可抑制TGF-β1刺激的NRK-49F细胞中纤连蛋白、I/IV型胶原和α-平滑肌肌动蛋白的上调。重要的是，盐霉素的抑制特性与Smad2/3和丝裂原活化蛋白激酶p38磷酸化的降低相关。总之，我们的数据表明盐霉素可能是一种用于对抗CKD患者肾纤维化的潜在药物。
