厚朴酚激活Sirtuin 3可以通过调节线粒体动力学和肾脏NF-κBTGF-β1/ Smad信号通路来减少单侧输尿管梗阻引起的肾脏炎症和纤维化。,International Journal of Molecular Sciences

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厚朴酚激活Sirtuin 3可以通过调节线粒体动力学和肾脏NF-κBTGF-β1/ Smad信号通路来减少单侧输尿管梗阻引起的肾脏炎症和纤维化。
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2020-01-08 , DOI: 10.3390/ijms21020402
Yi Quan ₁ , Woong Park ₁ , Jixiu Jin ₁ , Won Kim _{1,

2} , Sung Kwang Park _{1,

2} , Kyung Pyo Kang _{1,

2}

Affiliation

肾纤维化是所有进行性慢性肾脏疾病的共同特征。Sirtuin 3（SIRT3）是线粒体sirtuins之一，并在调节线粒体生物发生，氧化应激，脂肪酸代谢和衰老中发挥作用。近来，已发现厚朴酚（HKL）作为药物SIRT3激活剂通过增加SIRT3活性而对压力超负荷引起的心脏肥大具有保护作用。在这项研究中，我们调查了HKL作为SIRT3激活剂是否也通过SIRT3依赖的线粒体动力学调节和核因子-κB（NF-κB）/转化生长对单侧输尿管梗阻（UUO）引起的肾小管间质纤维化具有保护作用。因子-β1（TGF-β1）/ Smad信号通路。我们发现HKL减少了UUO诱导的小鼠肾小管损伤和细胞外基质（ECM）沉积增加。HKL还可以减少UUO肾脏和NRK-49F细胞中的成纤维细胞活化和增殖。最后，我们表明HKL治疗通过SIRT3依赖性作用降低了UUO诱导的线粒体裂变并促进了线粒体融合。综上所述，通过HKL处理激活SIRT3可能通过依赖线粒体动力学的SIRT3依赖性调节和NF-κB/TGF-β1/ Smad信号通路对UUO诱导的肾纤维化产生有益作用。

"点击查看英文标题和摘要"

Sirtuin 3 Activation by Honokiol Decreases Unilateral Ureteral Obstruction-Induced Renal Inflammation and Fibrosis via Regulation of Mitochondrial Dynamics and the Renal NF-κBTGF-β1/Smad Signaling Pathway.

Renal fibrosis is a common feature of all progressive chronic kidney diseases. Sirtuin 3(SIRT3) is one of the mitochondrial sirtuins, and plays a role in the regulation of mitochondrialbiogenesis, oxidative stress, fatty acid metabolism, and aging. Recently, honokiol (HKL), as apharmaceutical SIRT3 activator, has been observed to have a protective effect against pressureoverload-induced cardiac hypertrophy by increasing SIRT3 activity. In this study, we investigatedwhether HKL, as a SIRT3 activator, also has protective effects against unilateral ureteral obstruction(UUO)-induced renal tubulointerstitial fibrosis through SIRT3-dependent regulation ofmitochondrial dynamics and the nuclear factor-κB (NF-κB)/transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We found that HKL decreased the UUO-induced increase in tubularinjury and extracellular matrix (ECM) deposition in mice. HKL also decreased myofibroblastactivation and proliferation in UUO kidneys and NRK-49F cells. Finally, we showed that HKLtreatment decreased UUO-induced mitochondrial fission and promoted mitochondrial fusionthrough SIRT3-dependent effects. In conclusion, activation of SIRT3 via HKL treatment might havebeneficial effects on UUO-induced renal fibrosis through SIRT3-dependent regulation ofmitochondrial dynamics and the NF-κB/TGF-β1/Smad signaling pathway.

更新日期：2020-01-08

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