High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation.
High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation.
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高葡萄糖通过抑制 bFGF 调节 JNK 磷酸化来抑制伤口愈合中的人成纤维细胞迁移
DOI：
10.1371/journal.pone.0108182
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Jin LT
中科院分区：
文献类型：
--
作者：
Xuan YH;Huang BB;Tian HS;Chi LS;Duan YM;Wang X;Zhu ZX;Cai WH;Zhu YT;Wei TM;Ye HB;Cong WT;Jin LT
糖尿病（DM）的主要症状之一是伤口愈合延迟，其影响全世界的大量患者。然而，这种疾病背后的潜在机制仍然难以捉摸。皮肤伤口愈合需要一系列协调的过程，包括成纤维细胞增殖和迁移。本研究采用高糖刺激人包皮原代成纤维细胞模拟糖尿病，探讨糖尿病影响创面愈合的分子机制。结果表明，HG，在30 mM的浓度，延迟细胞迁移，但不细胞增殖。已知bFGF促进细胞迁移，其部分挽救HG对细胞迁移的影响。分子和细胞生物学研究表明，HG增强ROS的产生和抑制JNK磷酸化，但不影响Rac1的活性。JNK和Rac1的激活是已知的bFGF调节细胞迁移的重要。为了进一步证实糖尿病对皮肤修复的影响，我们建立了1型糖尿病大鼠模型，观察bFGF对正常和糖尿病大鼠皮肤修复的影响。此外，蛋白质组学研究确定了在HG应激成纤维细胞中膜联蛋白A2蛋白硝化的增加，并且该硝化通过bFGF信号传导的激活而受到保护。用FGFR1和JNK抑制剂处理延迟细胞迁移并增加膜联蛋白A2硝化水平，表明膜联蛋白A2硝化通过激活JNK由bFGF信号传导调节。与这些结果一起，我们的数据表明，HG介导的细胞迁移延迟与bFGF信号传导的抑制有关，特别是通过JNK抑制。
One of the major symptoms of diabetes mellitus (DM) is delayed wound healing, which affects large populations of patients worldwide. However, the underlying mechanism behind this illness remains elusive. Skin wound healing requires a series of coordinated processes, including fibroblast cell proliferation and migration. Here, we simulate DM by application of high glucose (HG) in human foreskin primary fibroblast cells to analyze the molecular mechanism of DM effects on wound healing. The results indicate that HG, at a concentration of 30 mM, delay cell migration, but not cell proliferation. bFGF is known to promote cell migration that partially rescues HG effects on cell migration. Molecular and cell biology studies demonstrated that HG enhanced ROS production and repressed JNK phosphorylation, but did not affect Rac1 activity. JNK and Rac1 activation were known to be important for bFGF regulated cell migration. To further confirm DM effects on skin repair, a type 1 diabetic rat model was established, and we observed the efficacy of bFGF on both normal and diabetic rat skin repair. Furthermore, proteomic studies identified an increase of Annexin A2 protein nitration in HG-stressed fibroblasts and the nitration was protected by activation of bFGF signaling. Treatment with FGFR1 and JNK inhibitors delayed cell migration and increased Annexin A2 nitration levels, indicating that Annexin A2 nitration is modulated by bFGF signaling via activation of JNK. Together with these results, our data suggests that the HG-mediated delay of cell migration is linked to the inhibition of bFGF signaling, specifically through JNK suppression.
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影响因子：
3.7
作者：
Kanazawa S;Fujiwara T;Matsuzaki S;Shingaki K;Taniguchi M;Miyata S;Tohyama M;Sakai Y;Yano K;Hosokawa K;Kubo T
通讯作者：
Kubo T
DOI：
10.1152/ajpendo.00570.2012
发表时间：
2013-04-01
影响因子：
5.1
作者：
Cong, Weitao;Ma, Weide;Cai, Lu
通讯作者：
Cai, Lu
影响因子：
6
作者：
Lerman, OZ;Galiano, RD;Gurtner, GC
通讯作者：
Gurtner, GC
影响因子：
56.9
作者：
Kimura, K;Ito, M;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
3.8
作者：
Park, Sun Joo;Jeon, You Jin
通讯作者：
Jeon, You Jin