High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation.
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 prolife...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4171528?pdf=render |
| _version_ | 1818263140857544704 |
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| author | Yuan Hu Xuan Bin Bin Huang Hai Shan Tian Li Sha Chi Yuan Meng Duan Xi Wang Zhong Xin Zhu Wan Hui Cai Yu Ting Zhu Tie Min Wei Hong Bo Ye Wei Tao Cong Li Tai Jin |
| author_facet | Yuan Hu Xuan Bin Bin Huang Hai Shan Tian Li Sha Chi Yuan Meng Duan Xi Wang Zhong Xin Zhu Wan Hui Cai Yu Ting Zhu Tie Min Wei Hong Bo Ye Wei Tao Cong Li Tai Jin |
| author_sort | Yuan Hu Xuan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T19:14:17Z |
| format | Article |
| id | doaj.art-63e42634c42e4362a07d7a02159831a2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T19:14:17Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-63e42634c42e4362a07d7a02159831a22022-12-22T00:14:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10818210.1371/journal.pone.0108182High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation.Yuan Hu XuanBin Bin HuangHai Shan TianLi Sha ChiYuan Meng DuanXi WangZhong Xin ZhuWan Hui CaiYu Ting ZhuTie Min WeiHong Bo YeWei Tao CongLi Tai JinOne 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.http://europepmc.org/articles/PMC4171528?pdf=render |
| spellingShingle | Yuan Hu Xuan Bin Bin Huang Hai Shan Tian Li Sha Chi Yuan Meng Duan Xi Wang Zhong Xin Zhu Wan Hui Cai Yu Ting Zhu Tie Min Wei Hong Bo Ye Wei Tao Cong Li Tai Jin High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation. PLoS ONE |
| title | High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation. |
| title_full | High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation. |
| title_fullStr | High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation. |
| title_full_unstemmed | High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation. |
| title_short | High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation. |
| title_sort | high glucose inhibits human fibroblast cell migration in wound healing via repression of bfgf regulating jnk phosphorylation |
| url | http://europepmc.org/articles/PMC4171528?pdf=render |
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