Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress
Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress
复制标题
成纤维细胞生长因子2通过抑制内质网应激减轻肾缺血再灌注损伤
DOI：
10.3389/fcell.2020.00147
复制
发表时间：
2020-03-24
影响因子：
5.5
通讯作者：
Li, Dequan
中科院分区：
文献类型：
--
作者：
Tan, Xiaohua;Tao, Qianyu;Li, Dequan
急性肾损伤（acute kidney injury，阿基）是一种严重的临床疾病，主要由肾缺血再灌注（ischemia-reperfusion，I/R）损伤、脓毒症和肾毒性药物引起。阿基的病理机制非常复杂，可能涉及氧化应激、炎症反应、自噬、凋亡和内质网（ER）应激。碱性成纤维细胞生长因子（FGF 2）是FGF家族的经典成员，在各种细胞过程中起着至关重要的作用，包括器官发育，伤口愈合和组织再生。然而，在过去的二十年里，很少有研究报道FGF 2在肾缺血损伤修复中的潜在治疗作用。本研究采用Sprague-Dawley细胞和NRK-52 E细胞研究FGF-2对肾I/R损伤的保护作用。我们的结果表明，FGF 2通过抑制过度的ER应激，显著减轻I/R损伤后肾组织的凋亡。此外，FGF 2还可减轻过氧化叔丁基（TBHP）损伤的NRK-52 E细胞的过度内质网应激和凋亡。值得注意的是，磷脂酰肌醇3-激酶（PI 3 K）选择性抑制剂LY 294002和丝裂原活化蛋白激酶激酶（MEK）选择性抑制剂U 0126在本研究中被用来检查FGF 2的保护机制。我们的体外实验结果证实，LY 294002和U 0126都在很大程度上消除了FGF 2的保护作用。综上所述，本研究的结果表明，FGF 2通过激活PI 3 K/AKT和MEK-ERK 1/2信号通路抑制过度的ER应激，从而减弱I/R诱导的肾上皮细胞凋亡。
Acute kidney injury (AKI) is a serious clinical disease that is mainly caused by renal ischemia-reperfusion (I/R) injury, sepsis, and nephrotoxic drugs. The pathologic mechanism of AKI is very complex and may involve oxidative stress, inflammatory response, autophagy, apoptosis, and endoplasmic reticulum (ER) stress. The basic fibroblast growth factor (FGF2) is a canonic member of the FGF family that plays a crucial role in various cellular processes, including organ development, wound healing, and tissue regeneration. However, few studies have reported the potential therapeutic effect of FGF2 in the repair of renal ischemic injury in the past two decades. In the present study, we investigated the protective effect of FGF2 on renal I/R injury using Sprague-Dawley and NRK-52E cells. Our results showed that FGF2 significantly attenuates the apoptosis of kidney tissues after I/R injury through the inhibition of excessive ER stress. Moreover, FGF2 also alleviated the excessive ER stress and apoptosis in cultured NRK-52E cells injured by tert-Butyl hydroperoxide (TBHP). Significantly, phosphatidylinositol 3-kinase (PI3K)-selective inhibitor LY294002 and mitogen-activated protein kinase kinase (MEK)-selective inhibitor U0126 were utilized in the present study to examine the protective mechanism of FGF2. Our in vitro experimental results confirmed that both LY294002 and U0126 largely abolished the protective effect of FGF2. Taken together, the findings of the present study indicated that FGF2 attenuates I/R-induced renal epithelial apoptosis by suppressing excessive ER stress via the activation of the PI3K/AKT and MEK-ERK1/2 signaling pathways.