rhMYDGF Alleviates I/R-induced Kidney Injury by Inhibiting Inflammation and Apoptosis via the Akt Pathway.
rhMYDGF Alleviates I/R-induced Kidney Injury by Inhibiting Inflammation and Apoptosis via the Akt Pathway.
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DOI：
10.1097/tp.0000000000004497
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发表时间：
2023-08-01
期刊：
影响因子：
6.2
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中科院分区：
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肾缺血再灌注损伤是影响肾移植术后预后的重要因素之一。近年来，髓源性生长因子（myeloid-derived growth factor，MYDGF）因其对心脏修复和保护心肌细胞免于细胞死亡的广泛有益作用而受到广泛关注。因此，我们推测重组人MYDGF（rhMYDGF）蛋白可能在保护肾I/R损伤中发挥重要作用。使用小鼠单侧I/R模型进行体内实验。通过腹腔注射rhMYDGF预处理小鼠以研究其肾脏保护的潜在机制。在体外实验中，我们建立了缺氧/复氧和H_2O_2处理模型，以rhMYDGF预处理细胞。检测组织和细胞中氧化应激、炎症及凋亡相关因子的表达水平。最后，探讨蛋白激酶B（Akt）通路在rhMYDGF肾保护机制中的作用。本研究发现，腹腔注射1.25 μg rhMYDGF可显著改善I/R小鼠肾功能，减轻氧化应激、炎症反应和细胞凋亡。对于人近端肾小管上皮细胞系和人肾细胞系，用0.3 μg/mL rhMYDGF预处理24 h显著下调氧化应激、炎症和通过Akt磷酸化的凋亡，这可以被LY 294002改善。rhMYDGF通过激活Akt通路减轻氧化应激、炎症和细胞凋亡，保护肾脏免受I/R损伤。
Renal ischemia/reperfusion (I/R) injury is one of the crucial factors affecting the outcome of renal transplantation. In recent years, myeloid-derived growth factor (MYDGF) has received a lot of attention for its extensive beneficial effects on cardiac repair and protection of cardiomyocytes from cell death. Therefore, we hypothesized that the recombinant human MYDGF (rhMYDGF) protein might play an essential role in safeguarding renal I/R injury. In vivo experiments were conducted using a mouse unilateral I/R model. Mice were pretreated with rhMYDGF by intraperitoneal injection to study the potential mechanism of renal protection. In vitro, we established hypoxia/reoxygenation and H2O2 treatment models to pretreat cells with rhMYDGF. The expression levels of oxidative stress, inflammation, and apoptosis-related factors in tissues and cells were detected. Finally, we explored the role of the protein kinase B (Akt) pathway in the renal protective mechanism of rhMYDGF. In this study, we found that intraperitoneal injection of 1.25 μg rhMYDGF could significantly improve renal function of I/R mice, and reduce oxidative stress, inflammation, and apoptosis. For the human proximal tubular epithelial cell line and human kidney cell line, pretreatment with 0.3 μg/mL rhMYDGF for 24 h significantly downregulated oxidative stress, inflammation, and apoptosis via the phosphorylation of Akt, which could be ameliorated by LY294002. rhMYDGF protects kidney from I/R injury by attenuating oxidative stress, inflammation, and apoptosis through the activation of the Akt pathway.