Advanced Glycation End Products and Activation of Toll-like Receptor-2 and -4 Induced Changes in Aquaporin-3 Expression in Mouse Keratinocytes
Prolonged inflammation and impaired re-epithelization are major contributing factors to chronic non-healing diabetic wounds; diabetes is also characterized by xerosis. Advanced glycation end products (AGEs), and the activation of toll-like receptors (TLRs), can trigger inflammatory responses. Aquapo...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1376 |
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| author | Yonghong Luo Rawipan Uaratanawong Vivek Choudhary Mary Hardin Catherine Zhang Samuel Melnyk Xunsheng Chen Wendy B. Bollag |
| author_facet | Yonghong Luo Rawipan Uaratanawong Vivek Choudhary Mary Hardin Catherine Zhang Samuel Melnyk Xunsheng Chen Wendy B. Bollag |
| author_sort | Yonghong Luo |
| collection | DOAJ |
| description | Prolonged inflammation and impaired re-epithelization are major contributing factors to chronic non-healing diabetic wounds; diabetes is also characterized by xerosis. Advanced glycation end products (AGEs), and the activation of toll-like receptors (TLRs), can trigger inflammatory responses. Aquaporin-3 (AQP3) plays essential roles in keratinocyte function and skin wound re-epithelialization/re-generation and hydration. Suberanilohydroxamic acid (SAHA), a histone deacetylase inhibitor, mimics the increased acetylation observed in diabetes. We investigated the effects of TLR2/TLR4 activators and AGEs on keratinocyte AQP3 expression in the presence and absence of SAHA. Primary mouse keratinocytes were treated with or without TLR2 agonist Pam<sub>3</sub>Cys-Ser-(Lys)<sub>4</sub> (PAM), TLR4 agonist lipopolysaccharide (LPS), or AGEs, with or without SAHA. We found that (1) PAM and LPS significantly upregulated AQP3 protein basally (without SAHA) and PAM downregulated AQP3 protein with SAHA; and (2) AGEs (100 µg/mL) increased AQP3 protein expression basally and decreased AQP3 levels with SAHA. PAM and AGEs produced similar changes in AQP3 expression, suggesting a common pathway or potential crosstalk between TLR2 and AGEs signaling. Our findings suggest that TLR2 activation and AGEs may be beneficial for wound healing and skin hydration under normal conditions via AQP3 upregulation, but that these pathways are likely deleterious in diabetes chronically through decreased AQP3 expression. |
| first_indexed | 2024-03-09T12:21:38Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:21:38Z |
| publishDate | 2023-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3a12a9cc5ee8446a8dd2892cab66a3892023-11-30T22:39:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242137610.3390/ijms24021376Advanced Glycation End Products and Activation of Toll-like Receptor-2 and -4 Induced Changes in Aquaporin-3 Expression in Mouse KeratinocytesYonghong Luo0Rawipan Uaratanawong1Vivek Choudhary2Mary Hardin3Catherine Zhang4Samuel Melnyk5Xunsheng Chen6Wendy B. Bollag7Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USAProlonged inflammation and impaired re-epithelization are major contributing factors to chronic non-healing diabetic wounds; diabetes is also characterized by xerosis. Advanced glycation end products (AGEs), and the activation of toll-like receptors (TLRs), can trigger inflammatory responses. Aquaporin-3 (AQP3) plays essential roles in keratinocyte function and skin wound re-epithelialization/re-generation and hydration. Suberanilohydroxamic acid (SAHA), a histone deacetylase inhibitor, mimics the increased acetylation observed in diabetes. We investigated the effects of TLR2/TLR4 activators and AGEs on keratinocyte AQP3 expression in the presence and absence of SAHA. Primary mouse keratinocytes were treated with or without TLR2 agonist Pam<sub>3</sub>Cys-Ser-(Lys)<sub>4</sub> (PAM), TLR4 agonist lipopolysaccharide (LPS), or AGEs, with or without SAHA. We found that (1) PAM and LPS significantly upregulated AQP3 protein basally (without SAHA) and PAM downregulated AQP3 protein with SAHA; and (2) AGEs (100 µg/mL) increased AQP3 protein expression basally and decreased AQP3 levels with SAHA. PAM and AGEs produced similar changes in AQP3 expression, suggesting a common pathway or potential crosstalk between TLR2 and AGEs signaling. Our findings suggest that TLR2 activation and AGEs may be beneficial for wound healing and skin hydration under normal conditions via AQP3 upregulation, but that these pathways are likely deleterious in diabetes chronically through decreased AQP3 expression.https://www.mdpi.com/1422-0067/24/2/1376toll-like receptor-2 (TLR2)TLR4advanced glycation end products (AGEs)aquaporin-3 (AQP3)histone deacetylase inhibitordiabetes |
| spellingShingle | Yonghong Luo Rawipan Uaratanawong Vivek Choudhary Mary Hardin Catherine Zhang Samuel Melnyk Xunsheng Chen Wendy B. Bollag Advanced Glycation End Products and Activation of Toll-like Receptor-2 and -4 Induced Changes in Aquaporin-3 Expression in Mouse Keratinocytes International Journal of Molecular Sciences toll-like receptor-2 (TLR2) TLR4 advanced glycation end products (AGEs) aquaporin-3 (AQP3) histone deacetylase inhibitor diabetes |
| title | Advanced Glycation End Products and Activation of Toll-like Receptor-2 and -4 Induced Changes in Aquaporin-3 Expression in Mouse Keratinocytes |
| title_full | Advanced Glycation End Products and Activation of Toll-like Receptor-2 and -4 Induced Changes in Aquaporin-3 Expression in Mouse Keratinocytes |
| title_fullStr | Advanced Glycation End Products and Activation of Toll-like Receptor-2 and -4 Induced Changes in Aquaporin-3 Expression in Mouse Keratinocytes |
| title_full_unstemmed | Advanced Glycation End Products and Activation of Toll-like Receptor-2 and -4 Induced Changes in Aquaporin-3 Expression in Mouse Keratinocytes |
| title_short | Advanced Glycation End Products and Activation of Toll-like Receptor-2 and -4 Induced Changes in Aquaporin-3 Expression in Mouse Keratinocytes |
| title_sort | advanced glycation end products and activation of toll like receptor 2 and 4 induced changes in aquaporin 3 expression in mouse keratinocytes |
| topic | toll-like receptor-2 (TLR2) TLR4 advanced glycation end products (AGEs) aquaporin-3 (AQP3) histone deacetylase inhibitor diabetes |
| url | https://www.mdpi.com/1422-0067/24/2/1376 |
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