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Fasting before or after wound injury accelerates wound healing through the activation of pro-angiogenic SMOC1 and SCG2
Healing of the chronic diabetic ulceration and large burns remains a clinical challenge. Therapeutic fasting has been shown to improve health. Our study tested whether fasting facilitates diabetic and burn wound healing and explored the underlying mechanism. Methods: The effects of fasting on diabet...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069085/ https://www.ncbi.nlm.nih.gov/pubmed/32206122 http://dx.doi.org/10.7150/thno.44115 |
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author | Luo, Ming-Jie Rao, Shan-Shan Tan, Yi-Juan Yin, Hao Hu, Xiong-Ke Zhang, Yan Liu, Yi-Wei Yue, Tao Chen, Ling-Jiao Li, Li Huang, Ya-Rong Qian, Yu-Xuan Liu, Zheng-Zhao Cao, Jia Wang, Zhen-Xing Luo, Zhong-Wei Wang, Yi-Yi Xia, Kun Tang, Si-Yuan Chen, Chun-Yuan Xie, Hui |
author_facet | Luo, Ming-Jie Rao, Shan-Shan Tan, Yi-Juan Yin, Hao Hu, Xiong-Ke Zhang, Yan Liu, Yi-Wei Yue, Tao Chen, Ling-Jiao Li, Li Huang, Ya-Rong Qian, Yu-Xuan Liu, Zheng-Zhao Cao, Jia Wang, Zhen-Xing Luo, Zhong-Wei Wang, Yi-Yi Xia, Kun Tang, Si-Yuan Chen, Chun-Yuan Xie, Hui |
author_sort | Luo, Ming-Jie |
collection | PubMed |
description | Healing of the chronic diabetic ulceration and large burns remains a clinical challenge. Therapeutic fasting has been shown to improve health. Our study tested whether fasting facilitates diabetic and burn wound healing and explored the underlying mechanism. Methods: The effects of fasting on diabetic and burn wound healing were evaluated by analyzing the rates of wound closure, re-epithelialization, scar formation, collagen deposition, skin cell proliferation and neovascularization using histological analyses and immunostaining. In vitro functional assays were conducted to assess fasting and refeeding on the angiogenic activities of endothelial cells. Transcriptome sequencing was employed to identify the differentially expressed genes in endothelial cells after fasting treatment and the role of the candidate genes in the fasting-induced promotion of angiogenesis was demonstrated. Results: Two times of 24-h fasting in a week after but especially before wound injury efficiently induced faster wound closure, better epidermal and dermal regeneration, less scar formation and higher level of angiogenesis in mice with diabetic or burn wounds. In vitro, fasting alone by serum deprivation did not increase, but rather reduced the abilities of endothelial cell to proliferate, migrate and form vessel-like tubes. However, subsequent refeeding did not merely rescue, but further augmented the angiogenic activities of endothelial cells. Transcriptome sequencing revealed that fasting itself, but not the following refeeding, induced a prominent upregulation of a variety of pro-angiogenic genes, including SMOC1 (SPARC related modular calcium binding 1) and SCG2 (secretogranin II). Immunofluorescent staining confirmed the increase of SMOC1 and SCG2 expression in both diabetic and burn wounds after fasting treatment. When the expression of SMOC1 or SCG2 was down-regulated, the fasting/refeeding-induced pro-angiogenic effects were markedly attenuated. Conclusion: This study suggests that fasting combined with refeeding, but not fasting solely, enhance endothelial angiogenesis through the activation of SMOC1 and SCG2, thus facilitating neovascularization and rapid wound healing. |
format | Online Article Text |
id | pubmed-7069085 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-70690852020-03-23 Fasting before or after wound injury accelerates wound healing through the activation of pro-angiogenic SMOC1 and SCG2 Luo, Ming-Jie Rao, Shan-Shan Tan, Yi-Juan Yin, Hao Hu, Xiong-Ke Zhang, Yan Liu, Yi-Wei Yue, Tao Chen, Ling-Jiao Li, Li Huang, Ya-Rong Qian, Yu-Xuan Liu, Zheng-Zhao Cao, Jia Wang, Zhen-Xing Luo, Zhong-Wei Wang, Yi-Yi Xia, Kun Tang, Si-Yuan Chen, Chun-Yuan Xie, Hui Theranostics Research Paper Healing of the chronic diabetic ulceration and large burns remains a clinical challenge. Therapeutic fasting has been shown to improve health. Our study tested whether fasting facilitates diabetic and burn wound healing and explored the underlying mechanism. Methods: The effects of fasting on diabetic and burn wound healing were evaluated by analyzing the rates of wound closure, re-epithelialization, scar formation, collagen deposition, skin cell proliferation and neovascularization using histological analyses and immunostaining. In vitro functional assays were conducted to assess fasting and refeeding on the angiogenic activities of endothelial cells. Transcriptome sequencing was employed to identify the differentially expressed genes in endothelial cells after fasting treatment and the role of the candidate genes in the fasting-induced promotion of angiogenesis was demonstrated. Results: Two times of 24-h fasting in a week after but especially before wound injury efficiently induced faster wound closure, better epidermal and dermal regeneration, less scar formation and higher level of angiogenesis in mice with diabetic or burn wounds. In vitro, fasting alone by serum deprivation did not increase, but rather reduced the abilities of endothelial cell to proliferate, migrate and form vessel-like tubes. However, subsequent refeeding did not merely rescue, but further augmented the angiogenic activities of endothelial cells. Transcriptome sequencing revealed that fasting itself, but not the following refeeding, induced a prominent upregulation of a variety of pro-angiogenic genes, including SMOC1 (SPARC related modular calcium binding 1) and SCG2 (secretogranin II). Immunofluorescent staining confirmed the increase of SMOC1 and SCG2 expression in both diabetic and burn wounds after fasting treatment. When the expression of SMOC1 or SCG2 was down-regulated, the fasting/refeeding-induced pro-angiogenic effects were markedly attenuated. Conclusion: This study suggests that fasting combined with refeeding, but not fasting solely, enhance endothelial angiogenesis through the activation of SMOC1 and SCG2, thus facilitating neovascularization and rapid wound healing. Ivyspring International Publisher 2020-02-19 /pmc/articles/PMC7069085/ /pubmed/32206122 http://dx.doi.org/10.7150/thno.44115 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Luo, Ming-Jie Rao, Shan-Shan Tan, Yi-Juan Yin, Hao Hu, Xiong-Ke Zhang, Yan Liu, Yi-Wei Yue, Tao Chen, Ling-Jiao Li, Li Huang, Ya-Rong Qian, Yu-Xuan Liu, Zheng-Zhao Cao, Jia Wang, Zhen-Xing Luo, Zhong-Wei Wang, Yi-Yi Xia, Kun Tang, Si-Yuan Chen, Chun-Yuan Xie, Hui Fasting before or after wound injury accelerates wound healing through the activation of pro-angiogenic SMOC1 and SCG2 |
title | Fasting before or after wound injury accelerates wound healing through the activation of pro-angiogenic SMOC1 and SCG2 |
title_full | Fasting before or after wound injury accelerates wound healing through the activation of pro-angiogenic SMOC1 and SCG2 |
title_fullStr | Fasting before or after wound injury accelerates wound healing through the activation of pro-angiogenic SMOC1 and SCG2 |
title_full_unstemmed | Fasting before or after wound injury accelerates wound healing through the activation of pro-angiogenic SMOC1 and SCG2 |
title_short | Fasting before or after wound injury accelerates wound healing through the activation of pro-angiogenic SMOC1 and SCG2 |
title_sort | fasting before or after wound injury accelerates wound healing through the activation of pro-angiogenic smoc1 and scg2 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069085/ https://www.ncbi.nlm.nih.gov/pubmed/32206122 http://dx.doi.org/10.7150/thno.44115 |
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