| Title |
Activation of α7nAChR Promotes Diabetic Wound Healing by Suppressing AGE-Induced TNF-α Production
|
|---|---|
| Published in |
Inflammation, December 2015
|
| DOI | 10.1007/s10753-015-0295-x |
| Pubmed ID | |
| Authors |
Miao-Wu Dong, Ming Li, Jie Chen, Tong-Tong Fu, Ke-Zhi Lin, Guang-Hua Ye, Jun-Ge Han, Xiang-Ping Feng, Xing-Biao Li, Lin-Sheng Yu, Yan-Yan Fan |
| Abstract |
Diabetes frequently presents accumulation of advanced glycation end products (AGEs), which might induce excessive TNF-α production from macrophages to cause impaired wound healing. Recent studies have shown that activation of α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages efficiently suppressed TNF-α synthesis. The aim of this study was to investigate the accumulation of AGEs in the wounds and determine whether PNU282987, an α7nAChR agonist, can improve wound repair by inhibiting AGE-mediated TNF-α production in a streptozotocin (STZ)-induced diabetic mouse model. Animals were assigned into four groups: wounded control group, wounded diabetic group, wounded diabetic group treated intraperitoneally with PNU282987, or wounded diabetic group treated intraperitoneally with vehicle. Compared with the non-diabetic control mice, the diabetic mice exhibited delayed wound healing that was characterized by elevated accumulation of AGEs, increased TNF-α level and macrophage infiltration, and decreased fibroblast number and collagen deposition at the late stage of repair. Besides, macrophages of diabetic wounds showed expression of α7nAChR. During late repair, PNU282987 treatment of diabetic mice significantly reduced the level of TNF-α, accelerated wound healing, and elevated fibroblast number and collagen deposition. To investigate the cellular mechanism of these observations, RAW 264.7 cells, a macrophage cell line, were incubated with AGEs in the presence or absence of PNU282987. TNF-α production from AGE-stimulated macrophages was significantly decreased by PNU282987 in a dose-dependent manner. Furthermore, PNU282987 significantly inhibited AGE-induced nuclear factor-κB (NF-κB) activation and receptor for AGE (RAGE) expression. These results strongly suggest that activating α7nAChR can promote diabetic wound healing by suppressing AGE-induced TNF-α production, which may be closely associated with the blockage of NF-κB activation in macrophages. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Japan | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 31 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 7 | 23% |
| Researcher | 4 | 13% |
| Student > Postgraduate | 3 | 10% |
| Student > Ph. D. Student | 3 | 10% |
| Student > Bachelor | 2 | 6% |
| Other | 6 | 19% |
| Unknown | 6 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 8 | 26% |
| Medicine and Dentistry | 3 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 10% |
| Nursing and Health Professions | 3 | 10% |
| Agricultural and Biological Sciences | 2 | 6% |
| Other | 6 | 19% |
| Unknown | 6 | 19% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 December 2015.
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#20,299,108
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Outputs from Inflammation
#714
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#326,291
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Outputs of similar age from Inflammation
#4
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