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Cobalt protoporphyrin promotes human keratinocyte migration under hyperglycemic conditions
BACKGROUND: Complete healing of diabetic wounds continues to be a clinically unmet need. Although robust therapies such as stem cell therapy and growth factor treatment are clinically applied, these treatments are costly for most diabetic wound patients. Therefore, a cheaper alternative is needed. C...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219158/ https://www.ncbi.nlm.nih.gov/pubmed/35739477 http://dx.doi.org/10.1186/s10020-022-00499-0 |
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author | Fang, Peng-Hsiang Lai, Ying-Ying Chen, Chih-Ling Wang, Hsin-Yu Chang, Ya-Ning Lin, Yung-Chang Yan, Yu-Ting Lai, Cheng-Hung Cheng, Bill |
author_facet | Fang, Peng-Hsiang Lai, Ying-Ying Chen, Chih-Ling Wang, Hsin-Yu Chang, Ya-Ning Lin, Yung-Chang Yan, Yu-Ting Lai, Cheng-Hung Cheng, Bill |
author_sort | Fang, Peng-Hsiang |
collection | PubMed |
description | BACKGROUND: Complete healing of diabetic wounds continues to be a clinically unmet need. Although robust therapies such as stem cell therapy and growth factor treatment are clinically applied, these treatments are costly for most diabetic wound patients. Therefore, a cheaper alternative is needed. Cobalt protoporphyrin (CoPP) has recently been demonstrated to promote tissue regeneration. In this study, the therapeutic benefits of CoPP in diabetic wound healing were examined. METHODS: An in vitro wound healing model that mimics re-epithelialization was established to examine the effect of CoPP on the migratory capability of human keratinocytes (HaCaT) in either normal glucose (NG) or high glucose (HG) media, as well as in the presence of either H(2)O(2) or lipopolysaccharide (LPS). At the end of the migration assays, cells were collected and subjected to Western blotting analysis and immunostaining. RESULTS: HaCaT were found to migrate significantly more slowly in the HG media compared to the NG media. CoPP treatment was found to enhance cell migration in HG media, but was found to decrease cell migration and proliferation when HaCaT were cultured in NG media. CoPP treatment induced high levels of expression of Nrf-2/HO-1 and FoxO1 in HaCaT cultured in either glucose concentration, although the FoxO1 expression was found to be significantly higher in HaCaT that underwent the migration assay in NG media compared to those in HG media. The higher level of FoxO1 expression seen in CoPP-treated HaCaT cultured in NG media resulted in upregulation of CCL20 and downregulation of TGFβ1. In contrast, HaCaT migrated in HG media were found to have high levels of expression of TGFβ1, and low levels of expression of CCL20. Interestingly, in the presence of H(2)O(2), CoPP-pretreated HaCaT cultured in either NG or HG media had similar expression level of Nrf-2/HO-1 and FoxO1 to each other. Moreover, the anti-apoptotic effect of CoPP pretreatment was noticed in HaCaT cultured in either glucose concentration. Additionally, CoPP pretreatment was shown to promote tight junction formation in HaCaT suffering from LPS-induced damage. CONCLUSIONS: CoPP enhances cell migratory capacity under hyperglycemic conditions, and protects cells from oxidative and LPS-induced cellular damage in HG media containing either H(2)O(2) or LPS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-022-00499-0. |
format | Online Article Text |
id | pubmed-9219158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-92191582022-06-24 Cobalt protoporphyrin promotes human keratinocyte migration under hyperglycemic conditions Fang, Peng-Hsiang Lai, Ying-Ying Chen, Chih-Ling Wang, Hsin-Yu Chang, Ya-Ning Lin, Yung-Chang Yan, Yu-Ting Lai, Cheng-Hung Cheng, Bill Mol Med Research Article BACKGROUND: Complete healing of diabetic wounds continues to be a clinically unmet need. Although robust therapies such as stem cell therapy and growth factor treatment are clinically applied, these treatments are costly for most diabetic wound patients. Therefore, a cheaper alternative is needed. Cobalt protoporphyrin (CoPP) has recently been demonstrated to promote tissue regeneration. In this study, the therapeutic benefits of CoPP in diabetic wound healing were examined. METHODS: An in vitro wound healing model that mimics re-epithelialization was established to examine the effect of CoPP on the migratory capability of human keratinocytes (HaCaT) in either normal glucose (NG) or high glucose (HG) media, as well as in the presence of either H(2)O(2) or lipopolysaccharide (LPS). At the end of the migration assays, cells were collected and subjected to Western blotting analysis and immunostaining. RESULTS: HaCaT were found to migrate significantly more slowly in the HG media compared to the NG media. CoPP treatment was found to enhance cell migration in HG media, but was found to decrease cell migration and proliferation when HaCaT were cultured in NG media. CoPP treatment induced high levels of expression of Nrf-2/HO-1 and FoxO1 in HaCaT cultured in either glucose concentration, although the FoxO1 expression was found to be significantly higher in HaCaT that underwent the migration assay in NG media compared to those in HG media. The higher level of FoxO1 expression seen in CoPP-treated HaCaT cultured in NG media resulted in upregulation of CCL20 and downregulation of TGFβ1. In contrast, HaCaT migrated in HG media were found to have high levels of expression of TGFβ1, and low levels of expression of CCL20. Interestingly, in the presence of H(2)O(2), CoPP-pretreated HaCaT cultured in either NG or HG media had similar expression level of Nrf-2/HO-1 and FoxO1 to each other. Moreover, the anti-apoptotic effect of CoPP pretreatment was noticed in HaCaT cultured in either glucose concentration. Additionally, CoPP pretreatment was shown to promote tight junction formation in HaCaT suffering from LPS-induced damage. CONCLUSIONS: CoPP enhances cell migratory capacity under hyperglycemic conditions, and protects cells from oxidative and LPS-induced cellular damage in HG media containing either H(2)O(2) or LPS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-022-00499-0. BioMed Central 2022-06-23 /pmc/articles/PMC9219158/ /pubmed/35739477 http://dx.doi.org/10.1186/s10020-022-00499-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Fang, Peng-Hsiang Lai, Ying-Ying Chen, Chih-Ling Wang, Hsin-Yu Chang, Ya-Ning Lin, Yung-Chang Yan, Yu-Ting Lai, Cheng-Hung Cheng, Bill Cobalt protoporphyrin promotes human keratinocyte migration under hyperglycemic conditions |
title | Cobalt protoporphyrin promotes human keratinocyte migration under hyperglycemic conditions |
title_full | Cobalt protoporphyrin promotes human keratinocyte migration under hyperglycemic conditions |
title_fullStr | Cobalt protoporphyrin promotes human keratinocyte migration under hyperglycemic conditions |
title_full_unstemmed | Cobalt protoporphyrin promotes human keratinocyte migration under hyperglycemic conditions |
title_short | Cobalt protoporphyrin promotes human keratinocyte migration under hyperglycemic conditions |
title_sort | cobalt protoporphyrin promotes human keratinocyte migration under hyperglycemic conditions |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219158/ https://www.ncbi.nlm.nih.gov/pubmed/35739477 http://dx.doi.org/10.1186/s10020-022-00499-0 |
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