bFGF alleviates diabetes-associated endothelial impairment by downregulating inflammation via S-nitrosylation pathway.
bFGF alleviates diabetes-associated endothelial impairment by downregulating inflammation via S-nitrosylation pathway.
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bFGF 通过 S-亚硝基化途径下调炎症，减轻糖尿病相关的内皮损伤
DOI：
10.1016/j.redox.2021.101904
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发表时间：
2021-05
期刊：
影响因子：
11.4
通讯作者：
Cong W
中科院分区：
文献类型：
--
作者：
Chen G;An N;Ye W;Huang S;Chen Y;Hu Z;Shen E;Zhu J;Gong W;Tong G;Zhu Y;Fang L;Cai C;Li X;Kim K;Jin L;Xiao J;Cong W
蛋白质s -亚硝基化是一种可逆的蛋白质修饰，涉及蛋白质功能的生理和病理生理调节。然而，失调的s -亚硝基化稳态与糖尿病血管并发症之间的关系尚不完全清楚。在这里，我们证明碱性成纤维细胞生长因子（bFGF）是s -亚硝基化稳态和炎症之间的关键调控环节，并减轻糖尿病的内皮功能障碍和血管生成缺陷。高血糖和高血脂使人脐静脉内皮细胞（HUVECs）内源性s -亚硝基化蛋白显著降低，包括抑制剂kappa B激酶β (IKKβC179)和转录因子p65 （p65C38）的s -亚硝基化，而bFGF联合处理可缓解这一现象。羧基ptio （c-PTIO）预处理，一氧化氮清除剂，消除bfgf介导的s -亚硝基化增加和内皮保护。同时，耐亚硝基化的IKKβC179S和p65C38S突变体加重了db/db小鼠和培养的高血糖和高脂血症HUVECs的内皮功能障碍。在机制上，bfgf介导的s -亚硝基化IKKβ和p65的增加归因于内皮一氧化氮合酶（eNOS）和硫氧还蛋白（Trx）活性增加的协同作用。综上所述，bFGF在高血糖和高脂血症下的内皮保护作用可部分归因于其通过s -亚硝基化途径抑制炎症的作用。
Protein S-nitrosylation is a reversible protein modification implicated in both physiological and pathophysiological regulation of protein function. However, the relationship between dysregulated S-nitrosylation homeostasis and diabetic vascular complications remains incompletely understood. Here, we demonstrate that basic fibroblast growth factor (bFGF) is a key regulatory link between S-nitrosylation homeostasis and inflammation, and alleviated endothelial dysfunction and angiogenic defects in diabetes. Subjecting human umbilical vein endothelial cells (HUVECs) to hyperglycemia and hyperlipidemia significantly decreased endogenous S-nitrosylated proteins, including S-nitrosylation of inhibitor kappa B kinase β (IKKβC179) and transcription factor p65 (p65C38), which was alleviated by bFGF co-treatment. Pretreatment with carboxy-PTIO (c-PTIO), a nitric oxide scavenger, abolished bFGF-mediated S-nitrosylation increase and endothelial protection. Meanwhile, nitrosylation-resistant IKKβC179S and p65C38S mutants exacerbated endothelial dysfunction in db/db mice, and in cultured HUVECs subjected to hyperglycemia and hyperlipidemia. Mechanistically, bFGF-mediated increase of S-nitrosylated IKKβ and p65 was attributed to synergistic effects of increased endothelial nitric oxide synthase (eNOS) and thioredoxin (Trx) activity. Taken together, the endothelial protective effect of bFGF under hyperglycemia and hyperlipidemia can be partially attributed to its role in suppressing inflammation via the S-nitrosylation pathway.
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影响因子：
82.9
作者：
通讯作者：
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影响因子：
7.7
作者：
Carvalho, MA;Ueno, M;Saad, MJA
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影响因子：
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DOI：
10.1152/ajplung.00463.2010
发表时间：
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