Gene Expression Linked to Reepithelialization of Human Skin Wounds
Our understanding of the regulatory processes of reepithelialization during wound healing is incomplete. In an attempt to map the genes involved in epidermal regeneration and differentiation, we measured gene expression in formalin-fixed, paraffin-embedded standardized epidermal wounds induced by th...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/15746 |
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| author | Magnus S. Ågren Thomas Litman Jens Ole Eriksen Peter Schjerling Michael Bzorek Lise Mette Rahbek Gjerdrum |
| author_facet | Magnus S. Ågren Thomas Litman Jens Ole Eriksen Peter Schjerling Michael Bzorek Lise Mette Rahbek Gjerdrum |
| author_sort | Magnus S. Ågren |
| collection | DOAJ |
| description | Our understanding of the regulatory processes of reepithelialization during wound healing is incomplete. In an attempt to map the genes involved in epidermal regeneration and differentiation, we measured gene expression in formalin-fixed, paraffin-embedded standardized epidermal wounds induced by the suction-blister technique with associated nonwounded skin using NanoString technology. The transcripts of 139 selected genes involved in clotting, immune response to tissue injury, signaling pathways, cell adhesion and proliferation, extracellular matrix remodeling, zinc transport and keratinocyte differentiation were evaluated. We identified 22 upregulated differentially expressed genes (DEGs) in descending order of fold change (<i>MMP1</i>, <i>MMP3</i>, <i>IL6</i>, <i>CXCL8</i>, <i>SERPINE1</i>, <i>IL1B</i>, <i>PTGS2</i>, <i>HBEGF</i>, <i>CXCL5</i>, <i>CXCL2</i>, <i>TIMP1</i>, <i>CYR61</i>, <i>CXCL1</i>, <i>MMP12</i>, <i>MMP9</i>, <i>HGF</i>, <i>CTGF</i>, <i>ITGB3</i>, <i>MT2A</i>, <i>FGF7</i>, <i>COL4A1</i> and <i>PLAUR</i>). The expression of the most upregulated gene, <i>MMP1</i>, correlated strongly with <i>MMP3</i> followed by <i>IL6</i> and <i>IL1B</i>. rhIL-1β, but not rhIL-6, exposure of cultured normal human epidermal keratinocytes and normal human dermal fibroblasts increased both <i>MMP1</i> mRNA and MMP-1 protein levels, as well as <i>TIMP1</i> mRNA levels. The increased <i>TIMP1</i> in wounds was validated by immunohistochemistry. The six downregulated DEGs (<i>COL7A1</i>, <i>MMP28</i>, <i>SLC39A2</i>, <i>FLG1</i>, <i>KRT10</i> and <i>FLG2</i>) were associated with epidermal maturation. <i>KLK8</i> showed the strongest correlation with <i>MKI67</i> mRNA levels and is a potential biomarker for keratinocyte proliferation. The observed gene expression changes correlate well with the current knowledge of physiological reepithelialization. Thus, the gene expression panel described in this paper could be used in patients with impaired healing to identify possible therapeutic targets. |
| first_indexed | 2024-03-09T16:20:05Z |
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| issn | 1661-6596 1422-0067 |
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| last_indexed | 2024-03-09T16:20:05Z |
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| spelling | doaj.art-d0b231b2f21c4c6fa14cc364c2e44d082023-11-24T15:27:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241574610.3390/ijms232415746Gene Expression Linked to Reepithelialization of Human Skin WoundsMagnus S. Ågren0Thomas Litman1Jens Ole Eriksen2Peter Schjerling3Michael Bzorek4Lise Mette Rahbek Gjerdrum5Department of Dermatology and Copenhagen Wound Healing Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, DenmarkDepartment of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, DenmarkDepartment of Pathology, Zealand University Hospital, 4000 Roskilde, DenmarkInstitute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital—Bispebjerg-Frederiksberg, 2400 Copenhagen, DenmarkDepartment of Pathology, Zealand University Hospital, 4000 Roskilde, DenmarkDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, DenmarkOur understanding of the regulatory processes of reepithelialization during wound healing is incomplete. In an attempt to map the genes involved in epidermal regeneration and differentiation, we measured gene expression in formalin-fixed, paraffin-embedded standardized epidermal wounds induced by the suction-blister technique with associated nonwounded skin using NanoString technology. The transcripts of 139 selected genes involved in clotting, immune response to tissue injury, signaling pathways, cell adhesion and proliferation, extracellular matrix remodeling, zinc transport and keratinocyte differentiation were evaluated. We identified 22 upregulated differentially expressed genes (DEGs) in descending order of fold change (<i>MMP1</i>, <i>MMP3</i>, <i>IL6</i>, <i>CXCL8</i>, <i>SERPINE1</i>, <i>IL1B</i>, <i>PTGS2</i>, <i>HBEGF</i>, <i>CXCL5</i>, <i>CXCL2</i>, <i>TIMP1</i>, <i>CYR61</i>, <i>CXCL1</i>, <i>MMP12</i>, <i>MMP9</i>, <i>HGF</i>, <i>CTGF</i>, <i>ITGB3</i>, <i>MT2A</i>, <i>FGF7</i>, <i>COL4A1</i> and <i>PLAUR</i>). The expression of the most upregulated gene, <i>MMP1</i>, correlated strongly with <i>MMP3</i> followed by <i>IL6</i> and <i>IL1B</i>. rhIL-1β, but not rhIL-6, exposure of cultured normal human epidermal keratinocytes and normal human dermal fibroblasts increased both <i>MMP1</i> mRNA and MMP-1 protein levels, as well as <i>TIMP1</i> mRNA levels. The increased <i>TIMP1</i> in wounds was validated by immunohistochemistry. The six downregulated DEGs (<i>COL7A1</i>, <i>MMP28</i>, <i>SLC39A2</i>, <i>FLG1</i>, <i>KRT10</i> and <i>FLG2</i>) were associated with epidermal maturation. <i>KLK8</i> showed the strongest correlation with <i>MKI67</i> mRNA levels and is a potential biomarker for keratinocyte proliferation. The observed gene expression changes correlate well with the current knowledge of physiological reepithelialization. Thus, the gene expression panel described in this paper could be used in patients with impaired healing to identify possible therapeutic targets.https://www.mdpi.com/1422-0067/23/24/15746wound healinggene expressionkeratinocytesfibroblastscytokinesmatrix metalloproteinases |
| spellingShingle | Magnus S. Ågren Thomas Litman Jens Ole Eriksen Peter Schjerling Michael Bzorek Lise Mette Rahbek Gjerdrum Gene Expression Linked to Reepithelialization of Human Skin Wounds International Journal of Molecular Sciences wound healing gene expression keratinocytes fibroblasts cytokines matrix metalloproteinases |
| title | Gene Expression Linked to Reepithelialization of Human Skin Wounds |
| title_full | Gene Expression Linked to Reepithelialization of Human Skin Wounds |
| title_fullStr | Gene Expression Linked to Reepithelialization of Human Skin Wounds |
| title_full_unstemmed | Gene Expression Linked to Reepithelialization of Human Skin Wounds |
| title_short | Gene Expression Linked to Reepithelialization of Human Skin Wounds |
| title_sort | gene expression linked to reepithelialization of human skin wounds |
| topic | wound healing gene expression keratinocytes fibroblasts cytokines matrix metalloproteinases |
| url | https://www.mdpi.com/1422-0067/23/24/15746 |
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