Cutaneous Epithelial to Mesenchymal Transition Activator ZEB1 Regulates Wound Angiogenesis and Closure in a Glycemic Status–Dependent Manner Article Swipe
Kanhaiya Singh
,
Mithun Sinha
,
Durba Pal
,
Saba Tabasum
,
Surya Gnyawali
,
Dolly K. Khona
,
Subendu Sarkar
,
Sujit K. Mohanty
,
Fidel Soto-Gonzalez
,
Savita Khanna
,
Sashwati Roy
,
Chandan K. Sen
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.2337/db19-0202
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.2337/db19-0202
Epithelial to mesenchymal transition (EMT) and wound vascularization are two critical interrelated processes that enable cutaneous wound healing. Zinc finger E-box binding homeobox 1 (ZEB1), primarily studied in the context of tumor biology, is a potent EMT activator. ZEB1 is also known to contribute to endothelial cell survival as well as stimulate tumor angiogenesis. The role of ZEB1 in cutaneous wounds was assessed using Zeb1+/− mice, as Zeb1−/− mice are not viable. Quantitative stable isotope labeling by amino acids in cell culture (SILAC) proteomics was used to elucidate the effect of elevated ZEB1, as noted during hyperglycemia. Under different glycemic conditions, ZEB1 binding to E-cadherin promoter was investigated using chromatin immunoprecipitation. Cutaneous wounding resulted in loss of epithelial marker E-cadherin with concomitant gain of ZEB1. The dominant proteins downregulated after ZEB1 overexpression functionally represented adherens junction pathway. Zeb1+/− mice exhibited compromised wound closure complicated by defective EMT and poor wound angiogenesis. Under hyperglycemic conditions, ZEB1 lost its ability to bind E-cadherin promoter. Keratinocyte E-cadherin, thus upregulated, resisted EMT required for wound healing. Diabetic wound healing was improved in ZEB+/− as well as in db/db mice subjected to ZEB1 knockdown. This work recognizes ZEB1 as a key regulator of cutaneous wound healing that is of particular relevance to diabetic wound complication.
Related Topics
Concepts
Adherens junction
Wound healing
Epithelial–mesenchymal transition
Angiogenesis
Chromatin immunoprecipitation
Downregulation and upregulation
Cancer research
Cell biology
Gene knockdown
Biology
Chemistry
Immunology
Cadherin
Cell
Apoptosis
Gene expression
Promoter
Biochemistry
Gene
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.2337/db19-0202
- https://diabetes.diabetesjournals.org/content/diabetes/68/11/2175.full.pdf
- OA Status
- bronze
- Cited By
- 61
- References
- 68
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2969997631
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2969997631Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.2337/db19-0202Digital Object Identifier
- Title
-
Cutaneous Epithelial to Mesenchymal Transition Activator ZEB1 Regulates Wound Angiogenesis and Closure in a Glycemic Status–Dependent MannerWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-08-22Full publication date if available
- Authors
-
Kanhaiya Singh, Mithun Sinha, Durba Pal, Saba Tabasum, Surya Gnyawali, Dolly K. Khona, Subendu Sarkar, Sujit K. Mohanty, Fidel Soto-Gonzalez, Savita Khanna, Sashwati Roy, Chandan K. SenList of authors in order
- Landing page
-
https://doi.org/10.2337/db19-0202Publisher landing page
- PDF URL
-
https://diabetes.diabetesjournals.org/content/diabetes/68/11/2175.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
-
https://diabetes.diabetesjournals.org/content/diabetes/68/11/2175.full.pdfDirect OA link when available
- Concepts
-
Adherens junction, Wound healing, Epithelial–mesenchymal transition, Angiogenesis, Chromatin immunoprecipitation, Downregulation and upregulation, Cancer research, Cell biology, Gene knockdown, Biology, Chemistry, Immunology, Cadherin, Cell, Apoptosis, Gene expression, Promoter, Biochemistry, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
61Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 4, 2024: 8, 2023: 13, 2022: 11, 2021: 14Per-year citation counts (last 5 years)
- References (count)
-
68Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.(SILAC) | 82 |
| abstract_inverted_index.(ZEB1), | 24 |
| abstract_inverted_index.ability | 157 |
| abstract_inverted_index.binding | 21, 102 |
| abstract_inverted_index.closure | 142 |
| abstract_inverted_index.context | 29 |
| abstract_inverted_index.culture | 81 |
| abstract_inverted_index.healing | 174, 200 |
| abstract_inverted_index.isotope | 74 |
| abstract_inverted_index.studied | 26 |
| abstract_inverted_index.viable. | 71 |
| abstract_inverted_index.Diabetic | 172 |
| abstract_inverted_index.ZEB+/− | 178 |
| abstract_inverted_index.adherens | 134 |
| abstract_inverted_index.assessed | 62 |
| abstract_inverted_index.biology, | 32 |
| abstract_inverted_index.critical | 10 |
| abstract_inverted_index.diabetic | 207 |
| abstract_inverted_index.dominant | 126 |
| abstract_inverted_index.elevated | 91 |
| abstract_inverted_index.glycemic | 99 |
| abstract_inverted_index.healing. | 17, 171 |
| abstract_inverted_index.homeobox | 22 |
| abstract_inverted_index.improved | 176 |
| abstract_inverted_index.junction | 135 |
| abstract_inverted_index.labeling | 75 |
| abstract_inverted_index.pathway. | 136 |
| abstract_inverted_index.promoter | 105 |
| abstract_inverted_index.proteins | 127 |
| abstract_inverted_index.required | 168 |
| abstract_inverted_index.resisted | 166 |
| abstract_inverted_index.resulted | 113 |
| abstract_inverted_index.survival | 47 |
| abstract_inverted_index.wounding | 112 |
| abstract_inverted_index.Cutaneous | 111 |
| abstract_inverted_index.Zeb1+/− | 64, 137 |
| abstract_inverted_index.chromatin | 109 |
| abstract_inverted_index.cutaneous | 15, 59, 198 |
| abstract_inverted_index.defective | 145 |
| abstract_inverted_index.different | 98 |
| abstract_inverted_index.elucidate | 87 |
| abstract_inverted_index.exhibited | 139 |
| abstract_inverted_index.primarily | 25 |
| abstract_inverted_index.processes | 12 |
| abstract_inverted_index.promoter. | 161 |
| abstract_inverted_index.regulator | 196 |
| abstract_inverted_index.relevance | 205 |
| abstract_inverted_index.stimulate | 51 |
| abstract_inverted_index.subjected | 185 |
| abstract_inverted_index.E-cadherin | 104, 119, 160 |
| abstract_inverted_index.Epithelial | 0 |
| abstract_inverted_index.activator. | 37 |
| abstract_inverted_index.contribute | 43 |
| abstract_inverted_index.epithelial | 117 |
| abstract_inverted_index.knockdown. | 188 |
| abstract_inverted_index.particular | 204 |
| abstract_inverted_index.proteomics | 83 |
| abstract_inverted_index.recognizes | 191 |
| abstract_inverted_index.transition | 3 |
| abstract_inverted_index.E-cadherin, | 163 |
| abstract_inverted_index.Zeb1−/− | 67 |
| abstract_inverted_index.complicated | 143 |
| abstract_inverted_index.compromised | 140 |
| abstract_inverted_index.concomitant | 121 |
| abstract_inverted_index.conditions, | 100, 153 |
| abstract_inverted_index.endothelial | 45 |
| abstract_inverted_index.mesenchymal | 2 |
| abstract_inverted_index.represented | 133 |
| abstract_inverted_index.Keratinocyte | 162 |
| abstract_inverted_index.Quantitative | 72 |
| abstract_inverted_index.functionally | 132 |
| abstract_inverted_index.interrelated | 11 |
| abstract_inverted_index.investigated | 107 |
| abstract_inverted_index.upregulated, | 165 |
| abstract_inverted_index.angiogenesis. | 53, 150 |
| abstract_inverted_index.complication. | 209 |
| abstract_inverted_index.downregulated | 128 |
| abstract_inverted_index.hyperglycemic | 152 |
| abstract_inverted_index.hyperglycemia. | 96 |
| abstract_inverted_index.overexpression | 131 |
| abstract_inverted_index.vascularization | 7 |
| abstract_inverted_index.immunoprecipitation. | 110 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 94 |
| corresponding_author_ids | https://openalex.org/A5103060166 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 12 |
| corresponding_institution_ids | https://openalex.org/I1283055418, https://openalex.org/I2802841970, https://openalex.org/I4394709130, https://openalex.org/I55769427 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7400000095367432 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.96395404 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |