TRPM7 in CHBP-induced renoprotection upon ischemia reperfusion-related injury.
TRPM7 in CHBP-induced renoprotection upon ischemia reperfusion-related injury.
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TRPM7 在 CHBP 诱导的缺血再灌注相关损伤的肾脏保护中的作用
DOI：
10.1038/s41598-018-22852-2
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发表时间：
2018-04-03
影响因子：
4.6
通讯作者：
Yang B
中科院分区：
文献类型：
--
作者：
Liu A;Wu J;Yang C;Wu Y;Zhang Y;Zhao F;Wang H;Yuan L;Song L;Zhu T;Fan Y;Yang B
瞬时受体电位美拉抑素7 （TRPM7）是一种膜离子通道和激酶。TRPM7在肾脏中大量表达，并因缺血再灌注（IR）损伤而上调。我们之前的研究表明，环螺旋B肽（CHBP）可改善肾ir相关损伤，但其潜在机制尚未明确。肾小管上皮细胞（TCMK-1和HK-2）通过12 ~ 24小时缺氧(H)和2 ~ 24小时再氧合(R)，以及小鼠肾脏缺血30分钟和再灌注12 ~ 7天，建立了ir相关损伤。TCMK-1细胞中TRPM7样电流升高，体外黄素模型中TRPM7 mRNA和蛋白表达升高，CHBP可使其逆转。TRPM7还分别与LDH、HMGB1、caspase-3、Bax/Bcl-2、炎症、凋亡、小管间质损伤和肾功能呈正相关。此外，沉默TRPM7可改善两种模型的损伤参数、肾脏组织学和功能。特异性TRPM7激动剂缓激肽可加重HR诱导的TCMK-1细胞损伤，并部分阻断CHBP的肾保护作用。综上所述，TRPM7不仅参与ir相关损伤，还参与chbp诱导的肾保护，通过其离子通道影响炎症和细胞凋亡。因此，TRPM7可能是红外诱导的急性肾损伤的潜在生物标志物。
Transient receptor potential melastatin 7 (TRPM7) is a membrane ion channel and kinase. TRPM7 was abundantly expressed in the kidney, and up-regulated by ischemia reperfusion (IR) injury. Our previous studies showed that cyclic helix B peptide (CHBP) improved renal IR-related injury, but its underlying mechanism is not well defined. IR-related injury was established in renal tubular epithelial cells (TCMK-1 and HK-2) via 12 to 24-h hypoxia (H) followed by 2-24 h reoxygenation (R), and in mouse kidneys subjected to 30-min ischemia and 12-h to 7-day reperfusion. TRPM7-like current in TCMK-1 cells, TRPM7 mRNA and protein in thein vitroandin vivomodels were increased, but reversed by CHBP. TRPM7 was also positively associated with LDH, HMGB1, caspase-3, Bax/Bcl-2, inflammation, apoptosis, tubulointerstitial damage and renal function respectively. Furthermore, silencing TRPM7 improved injury parameters, renal histology and function in the both models. Specific TRPM7 agonist, bradykinin, exaggerated HR induced injury in TCMK-1 cells, and partially blocked the renoprotection of CHBP as well. In conclusion, TRPM7 is involved not only in IR-related injury, but also CHBP-induced renoprotection, which are through its ion channel and subsequent affects inflammation and apoptosis. Therefore, TRPM7 could be a potential biomarker for IR-induced acute kidney injury.
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影响因子：
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