Single-Cell Transcriptomics Unveils the Mechanistic Role of FOSL1 in Cutaneous Wound Healing
<b>Background:</b> The skin, a complex organ vital for protecting the body against environmental challenges, undergoes a multifaceted wound healing process involving hemostasis, inflammation, proliferation, and remodeling. The transcription factor FOSL1 has been implicated in various cel...
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2025-05-01
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| author | Jingbi Meng Ge Zheng Yinli Luo Ling Ge Zhiqing Liu Wenhua Huang Meitong Jin Yanli Kong Shanhua Xu Zhehu Jin Longquan Pi |
| author_facet | Jingbi Meng Ge Zheng Yinli Luo Ling Ge Zhiqing Liu Wenhua Huang Meitong Jin Yanli Kong Shanhua Xu Zhehu Jin Longquan Pi |
| author_sort | Jingbi Meng |
| collection | DOAJ |
| description | <b>Background:</b> The skin, a complex organ vital for protecting the body against environmental challenges, undergoes a multifaceted wound healing process involving hemostasis, inflammation, proliferation, and remodeling. The transcription factor FOSL1 has been implicated in various cellular processes crucial for wound healing, including cell cycle regulation, differentiation, and apoptosis. We hypothesize that FOSL1 is a key regulator of wound healing processes. <b>Objective:</b> The objective of this study was to investigate the role of FOSL1 in cutaneous wound healing, identify the core signaling pathways involved, and assess FOSL1′s potential as a therapeutic target. <b>Method:</b> We utilized datasets from the Gene Expression Omnibus (GEO) and applied the ‘limma’ package to discern differentially expressed genes (DEGs). We intersected these DEGs with transcription factor-associated genes from the TRRUST database. Subsequently, we constructed Protein–Protein Interaction (PPI) networks via the STRING database. Machine learning algorithms were instrumental in identifying pivotal genes, a finding corroborated through animal modeling and Western blot analysis of tissue samples. To elucidate biological pathway activities from gene expression data, we deployed the ‘PROGENy’ package, complemented by machine learning for precise pathway identification. Furthermore, Gene Set Variation Analysis (GSVA) was executed across Hallmark, biological process (BP), molecular function (MF), and cellular component (CC) categories to deepen our understanding of the wound healing process. <b>Results:</b> Our analysis revealed that FOSL1 is significantly upregulated in wounded skin. The Mitogen-Activated Protein Kinase (MAPK) and Epidermal Growth Factor Receptor (EGFR) pathways were identified as significantly associated with FOSL1. GSVA identifies critical changes in wound healing processes like ‘apical junction’ and ‘epithelial–mesenchymal transition.’ The upregulation of ‘cytoplasm organization’ and ‘response to gravity’ suggests roles in cellular adaptation. Molecular function analysis indicates alterations in ‘cytokeratin filaments’ and ‘growth factor binding,’ which are key for tissue repair. Cellular component shifts in ‘postsynaptic cytosol’ and ‘endoplasmic reticulum’ suggest changes in communication and protein processing. <b>Conclusions:</b> Our study identifies FOSL1 as a potential regulator of cutaneous wound healing through its modulation of cellular signaling pathways, offering novel insights into the molecular control of tissue repair. These findings highlight FOSL1 as a promising therapeutic target to accelerate healing in chronic or impaired wounds. |
| format | Article |
| id | doaj-art-1bc35e794a43404f8a7e18ab4e928913 |
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| publishDate | 2025-05-01 |
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| spelling | doaj-art-1bc35e794a43404f8a7e18ab4e9289132025-08-20T02:24:26ZengMDPI AGBiomedicines2227-90592025-05-01136133010.3390/biomedicines13061330Single-Cell Transcriptomics Unveils the Mechanistic Role of FOSL1 in Cutaneous Wound HealingJingbi Meng0Ge Zheng1Yinli Luo2Ling Ge3Zhiqing Liu4Wenhua Huang5Meitong Jin6Yanli Kong7Shanhua Xu8Zhehu Jin9Longquan Pi10Department of Central Laboratory, Yanbian University Hospital, Yanji 133001, ChinaDepartment of Central Laboratory, Yanbian University Hospital, Yanji 133001, ChinaDepartment of Dermatology, Yanbian University Hospital, Yanji 133001, ChinaDepartment of Dermatology, Yanbian University Hospital, Yanji 133001, ChinaDepartment of Dermatology, Yanbian University Hospital, Yanji 133001, ChinaDepartment of Central Laboratory, Yanbian University Hospital, Yanji 133001, ChinaDepartment of Dermatology, Yanbian University Hospital, Yanji 133001, ChinaDepartment of Dermatology, Yanbian University Hospital, Yanji 133001, ChinaDepartment of Anesthesia, Yanbian University Hospital, Yanji 133001, ChinaDepartment of Dermatology, Yanbian University Hospital, Yanji 133001, ChinaDepartment of Dermatology, Yanbian University Hospital, Yanji 133001, China<b>Background:</b> The skin, a complex organ vital for protecting the body against environmental challenges, undergoes a multifaceted wound healing process involving hemostasis, inflammation, proliferation, and remodeling. The transcription factor FOSL1 has been implicated in various cellular processes crucial for wound healing, including cell cycle regulation, differentiation, and apoptosis. We hypothesize that FOSL1 is a key regulator of wound healing processes. <b>Objective:</b> The objective of this study was to investigate the role of FOSL1 in cutaneous wound healing, identify the core signaling pathways involved, and assess FOSL1′s potential as a therapeutic target. <b>Method:</b> We utilized datasets from the Gene Expression Omnibus (GEO) and applied the ‘limma’ package to discern differentially expressed genes (DEGs). We intersected these DEGs with transcription factor-associated genes from the TRRUST database. Subsequently, we constructed Protein–Protein Interaction (PPI) networks via the STRING database. Machine learning algorithms were instrumental in identifying pivotal genes, a finding corroborated through animal modeling and Western blot analysis of tissue samples. To elucidate biological pathway activities from gene expression data, we deployed the ‘PROGENy’ package, complemented by machine learning for precise pathway identification. Furthermore, Gene Set Variation Analysis (GSVA) was executed across Hallmark, biological process (BP), molecular function (MF), and cellular component (CC) categories to deepen our understanding of the wound healing process. <b>Results:</b> Our analysis revealed that FOSL1 is significantly upregulated in wounded skin. The Mitogen-Activated Protein Kinase (MAPK) and Epidermal Growth Factor Receptor (EGFR) pathways were identified as significantly associated with FOSL1. GSVA identifies critical changes in wound healing processes like ‘apical junction’ and ‘epithelial–mesenchymal transition.’ The upregulation of ‘cytoplasm organization’ and ‘response to gravity’ suggests roles in cellular adaptation. Molecular function analysis indicates alterations in ‘cytokeratin filaments’ and ‘growth factor binding,’ which are key for tissue repair. Cellular component shifts in ‘postsynaptic cytosol’ and ‘endoplasmic reticulum’ suggest changes in communication and protein processing. <b>Conclusions:</b> Our study identifies FOSL1 as a potential regulator of cutaneous wound healing through its modulation of cellular signaling pathways, offering novel insights into the molecular control of tissue repair. These findings highlight FOSL1 as a promising therapeutic target to accelerate healing in chronic or impaired wounds.https://www.mdpi.com/2227-9059/13/6/1330EGFR pathwayFOSL1MAPK pathwaysingle-cell sequencingwound healing |
| spellingShingle | Jingbi Meng Ge Zheng Yinli Luo Ling Ge Zhiqing Liu Wenhua Huang Meitong Jin Yanli Kong Shanhua Xu Zhehu Jin Longquan Pi Single-Cell Transcriptomics Unveils the Mechanistic Role of FOSL1 in Cutaneous Wound Healing Biomedicines EGFR pathway FOSL1 MAPK pathway single-cell sequencing wound healing |
| title | Single-Cell Transcriptomics Unveils the Mechanistic Role of FOSL1 in Cutaneous Wound Healing |
| title_full | Single-Cell Transcriptomics Unveils the Mechanistic Role of FOSL1 in Cutaneous Wound Healing |
| title_fullStr | Single-Cell Transcriptomics Unveils the Mechanistic Role of FOSL1 in Cutaneous Wound Healing |
| title_full_unstemmed | Single-Cell Transcriptomics Unveils the Mechanistic Role of FOSL1 in Cutaneous Wound Healing |
| title_short | Single-Cell Transcriptomics Unveils the Mechanistic Role of FOSL1 in Cutaneous Wound Healing |
| title_sort | single cell transcriptomics unveils the mechanistic role of fosl1 in cutaneous wound healing |
| topic | EGFR pathway FOSL1 MAPK pathway single-cell sequencing wound healing |
| url | https://www.mdpi.com/2227-9059/13/6/1330 |
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