Transforming growth factor-β1 negatively regulates SOCS7 via EGR1 during wound healing

Abstract Background TGF-β1 promotes keratinocyte migration and re-epithelialization of cutaneous wounds during the wound healing process. Decreased SOCS7 expression has been associated with increased healing potential. However, the relationship between TGF-β1 and SOCS7 in wound re-epithelialization...

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Main Authors: Xiao Feng, Wei Feng, Yu Ji, Tingting Jin, Jingyu Li, Jincai Guo
Format: Article
Language:English
Published: BMC 2022-06-01
Series:Cell Communication and Signaling
Subjects:
Online Access:https://doi.org/10.1186/s12964-022-00893-5
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author Xiao Feng
Wei Feng
Yu Ji
Tingting Jin
Jingyu Li
Jincai Guo
author_facet Xiao Feng
Wei Feng
Yu Ji
Tingting Jin
Jingyu Li
Jincai Guo
author_sort Xiao Feng
collection DOAJ
description Abstract Background TGF-β1 promotes keratinocyte migration and re-epithelialization of cutaneous wounds during the wound healing process. Decreased SOCS7 expression has been associated with increased healing potential. However, the relationship between TGF-β1 and SOCS7 in wound re-epithelialization remains unclear. Objectives To investigate the relationship between TGF-β1 and SOCS7 in the re-epithelialization of keratinocytes during skin wound healing. Methods The expression of SOCS7 under different concentrations of TGF-β1 was detected by WB and qPCR. The migration ability of keratinocytes was detected by scratch and Transwell assay. Protein interactions were detected by ChIP and luciferase assay. The effect of SOCS7 on skin healing in mice was detected in animal model. Results In this study, we found that SOCS7 was downregulated by TGF-β1 and that overexpression of SOCS7 led to suppression of TGF-β1-induced keratinocyte migration through inhibition of the PI3K/AKT and MEK/ERK pathways. Also, TGF-β1 negatively regulated SOCS7 expression at the transcriptional level through the binding of EGR1 to the EGR1/SP1 overlapping binding sites in the SOCS7 promoter. Conclusion Taken together, our findings show that TGF-β1-induced EGR1 expression is required for repression of SOCS7, which promotes keratinocyte migration and re-epithelialization during wound healing. Finally, our study identifies the TGF-β1/EGR1/SOCS7 pathway as a potential therapeutic target to promote wound healing. Video Abstract
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spelling doaj.art-3c09ff29b5e14da8b639d24b78f078f22022-12-22T02:33:13ZengBMCCell Communication and Signaling1478-811X2022-06-0120111210.1186/s12964-022-00893-5Transforming growth factor-β1 negatively regulates SOCS7 via EGR1 during wound healingXiao Feng0Wei Feng1Yu Ji2Tingting Jin3Jingyu Li4Jincai Guo5Department of Plastic Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical CollegeDepartment of Plastic Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical CollegeDepartment of Plastic Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical CollegeDepartment of Plastic Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical CollegeDepartment of Plastic Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical CollegeDepartment of Plastic Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical CollegeAbstract Background TGF-β1 promotes keratinocyte migration and re-epithelialization of cutaneous wounds during the wound healing process. Decreased SOCS7 expression has been associated with increased healing potential. However, the relationship between TGF-β1 and SOCS7 in wound re-epithelialization remains unclear. Objectives To investigate the relationship between TGF-β1 and SOCS7 in the re-epithelialization of keratinocytes during skin wound healing. Methods The expression of SOCS7 under different concentrations of TGF-β1 was detected by WB and qPCR. The migration ability of keratinocytes was detected by scratch and Transwell assay. Protein interactions were detected by ChIP and luciferase assay. The effect of SOCS7 on skin healing in mice was detected in animal model. Results In this study, we found that SOCS7 was downregulated by TGF-β1 and that overexpression of SOCS7 led to suppression of TGF-β1-induced keratinocyte migration through inhibition of the PI3K/AKT and MEK/ERK pathways. Also, TGF-β1 negatively regulated SOCS7 expression at the transcriptional level through the binding of EGR1 to the EGR1/SP1 overlapping binding sites in the SOCS7 promoter. Conclusion Taken together, our findings show that TGF-β1-induced EGR1 expression is required for repression of SOCS7, which promotes keratinocyte migration and re-epithelialization during wound healing. Finally, our study identifies the TGF-β1/EGR1/SOCS7 pathway as a potential therapeutic target to promote wound healing. Video Abstracthttps://doi.org/10.1186/s12964-022-00893-5TGF-β1SOCS7EGR1KeratinocytesWound healing
spellingShingle Xiao Feng
Wei Feng
Yu Ji
Tingting Jin
Jingyu Li
Jincai Guo
Transforming growth factor-β1 negatively regulates SOCS7 via EGR1 during wound healing
Cell Communication and Signaling
TGF-β1
SOCS7
EGR1
Keratinocytes
Wound healing
title Transforming growth factor-β1 negatively regulates SOCS7 via EGR1 during wound healing
title_full Transforming growth factor-β1 negatively regulates SOCS7 via EGR1 during wound healing
title_fullStr Transforming growth factor-β1 negatively regulates SOCS7 via EGR1 during wound healing
title_full_unstemmed Transforming growth factor-β1 negatively regulates SOCS7 via EGR1 during wound healing
title_short Transforming growth factor-β1 negatively regulates SOCS7 via EGR1 during wound healing
title_sort transforming growth factor β1 negatively regulates socs7 via egr1 during wound healing
topic TGF-β1
SOCS7
EGR1
Keratinocytes
Wound healing
url https://doi.org/10.1186/s12964-022-00893-5
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AT tingtingjin transforminggrowthfactorb1negativelyregulatessocs7viaegr1duringwoundhealing
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