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Piezo1 通过介导细胞凋亡和线粒体功能障碍促进肾纤维化的发生和进展。

Piezo1 facilitates the initiation and progression of renal fibrosis by mediating cell apoptosis and mitochondrial dysfunction.

机构信息

Urodynamic Centre, Henan Joint International Pediatric Urodynamic Laboratory and Department of Urology, The First Affiliated Hospital of Zhengzhou University, Henan, China.

Department of Urology, Xinyang Central Hospital, Xinyang, Henan, China.

出版信息

Ren Fail. 2024 Dec;46(2):2415519. doi: 10.1080/0886022X.2024.2415519. Epub 2024 Nov 4.

Abstract

Renal fibrosis is the major pathological changes of Chronic kidney disease (CKD). Piezo1, a mechanical sensitive ion channel, is implicated in organ fibrosis. However, the precise role of Piezo1 in CKD fibrosis is unknown. The aims of this study were to identify that the role of Piezo1 in CKD fibrosis and its potential involvement of mitochondrial dysfunction. We performed the study with the Piezo1 agonist Yoda1, Bax inhibitor BAI1, Piezo1 inhibitor GsMTx4 and detected the injury, fibrosis, apoptosis markers and mitochondrial dysfunction. The results showed that the levels of apoptosis, mitochondrial dysfunction, injury and fibrosis increased in TCMK-1 cells after treatment with Yoda1. However, these changes that induced by Yoda1 were relieved by BAI1. Similarly, inhibition Piezo1 with GsMTx4 also partly relieved the renal injury, renal fibrosis, apoptosis and mitochondrial dysfunction and vitro. In conclusion, we found Piezo1 promoted the initiation and development of renal fibrosis and inhibiting Piezo1 improved the fibrosis.

摘要

肾脏纤维化是慢性肾脏病(CKD)的主要病理变化。Piezo1 是一种机械敏感性离子通道,与器官纤维化有关。然而,Piezo1 在 CKD 纤维化中的确切作用尚不清楚。本研究旨在确定 Piezo1 在 CKD 纤维化中的作用及其潜在的线粒体功能障碍。我们用 Piezo1 激动剂 Yoda1、Bax 抑制剂 BAI1、Piezo1 抑制剂 GsMTx4 进行了研究,并检测了损伤、纤维化、凋亡标志物和线粒体功能障碍。结果表明,Yoda1 处理后 TCMK-1 细胞的凋亡、线粒体功能障碍、损伤和纤维化水平增加。然而,BAI1 缓解了 Yoda1 诱导的这些变化。同样,用 GsMTx4 抑制 Piezo1 也部分缓解了体外的肾损伤、肾纤维化、凋亡和线粒体功能障碍。总之,我们发现 Piezo1 促进了肾脏纤维化的发生和发展,抑制 Piezo1 可改善纤维化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f06/11536639/823a9f7e3ba1/IRNF_A_2415519_UF0001_C.jpg

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