CoChat
Sign Up
Cited by 232Wound Healing and TreatmentsTGF-β signaling in diseasesCancer Cells and Metastasis

Epithelial‐to‐mesenchymal transition in cutaneous wound healing: Where we are and where we are heading

Open access
Haensel, Daniel, Dai, Xing·2018·Developmental Dynamics
DOI 10.1002/dvdy.24561PMC PMC5809211
Open this paper in CoChat — free accountOpen PDF

Abstract

Cutaneous wound healing occurs in distinct yet overlapping steps with the end goal of reforming a stratified epithelium to restore epidermal barrier function. A key component of this process is re-epithelialization, which involves the proliferation and migration of epidermal keratinocytes surrounding the wound. This spatiotemporally controlled process resembles aspects of the epithelial-to-mesenchymal transition (EMT) process and is thus proposed to involve a partial EMT. Here, we review current literature on the cellular and molecular changes that occur during, and the known or potential regulatory factors of cutaneous wound re-epithelialization and EMT to highlight their similarities and differences. We also discuss possible future directions toward a better understanding of the underlying regulatory mechanisms with implications for developing new therapeutics to improve wound repair in humans. Developmental Dynamics 247:473-480, 2018. © 2017 Wiley Periodicals, Inc.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/dvdy.24561

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • HSEs may represent a wound regeneration or development model because of their EMT features and inappropriate expression of KRT14.

    “Our results also suggest that HSEs may represent a wound regeneration or development model because of their EMT features and inappropriate expression of KRT14.51”

    From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [51]

    The Conclusions and perspectives section says wound re-epithelialization shares cellular and molecular changes with EMT and discusses a possible role for EMT-like states in regeneration. It does not address HSEs or inappropriate KRT14 expression, so it cannot support those specific features of the citing authors’ proposed model. The supplied passages have no page numbers. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 50

  1. Aragona M Dekoninck S Rulands S Lenglez S Mascre G Simons BD Blanpain C 2017 Defining stem cell dynamics and migration during wound healing in mouse skin epidermis Nat Commun 8 14684 28248284 PMC5339881
  2. Arnoux V Nassour M L’Helgoualc’h A Hipskind R Savagner P 2008 Erk5 controls slug expression and keratinocyte activation during wound healing Mol Biol Cell 19 4738 4749 18716062 PMC2575153
  3. Arwert EN Hoste E Watt FM 2012 Epithelial stem cells, wound healing and cancer Nat Rev Cancer 12 170 180 22362215
  4. Beaudry VG Ihrie RA Jacobs SB Nguyen B Pathak N Park E Attardi LD 2010 Loss of the desmosomal component perp impairs wound healing in vivo Dermatol Res Pract 2010 759731 20628490 PMC2902749
  5. Bielefeld KA Amini-Nik S Alman BA 2013 Cutaneous wound healing: recruiting developmental pathways for regeneration Cell Mol Life Sci 70 2059 2081 23052205 PMC3663196
  6. Brabletz S Brabletz T 2010 The ZEB/miR-200 feedback loop–a motor of cellular plasticity in development and cancer? EMBO Rep 11 670 677 20706219 PMC2933868
  7. Cheng F Shen Y Mohanasundaram P Lindstrom M Ivaska J Ny T Eriksson JE 2016 Vimentin coordinates fibroblast proliferation and keratinocyte differentiation in wound healing via TGF-beta-Slug signaling Proc Natl Acad Sci U S A 113 E4320 4327 27466403 PMC4968728
  8. Chigurupati S Arumugam TV Son TG Lathia JD Jameel S Mughal MR Tang SC Jo DG Camandola S Giunta M Rakova I McDonnell N Miele L Mattson MP Poosala S 2007 Involvement of notch signaling in wound healing PLoS One 2 e1167 18000539 PMC2048753
  9. Coulombe P 1997 Towards a moleclar definition of keratinocyte activation after acute injury to stratified epithelia Biochemical and Biophysical Reseach Communications 236 231 238 9240415
  10. Coulombe PA 2003 Wound epithelialization: accelerating the pace of discovery J Invest Dermatol 121 219 230 12880412
  11. Eming SA Martin P Tomic-Canic M 2014 Wound repair and regeneration: mechanisms, signaling, and translation Sci Transl Med 6 1 16 PMC4973620 25473038
  12. Ferguson MW O’Kane S 2004 Scar-free healing: from embryonic mechanisms to adult therapeutic intervention Philos Trans R Soc Lond B Biol Sci 359 839 850 15293811 PMC1693363
  13. Garrod DR Berika MY Bardsley WF Holmes D Tabernero L 2005 Hyper-adhesion in desmosomes: its regulation in wound healing and possible relationship to cadherin crystal structure J Cell Sci 118 5743 5754 16303847
  14. Gawronska-Kozak B Grabowska A Kur-Piotrowska A Kopcewicz M 2016 Foxn1 Transcription Factor Regulates Wound Healing of Skin through Promoting Epithelial-Mesenchymal Transition PLoS One 11 e0150635 26938103 PMC4777299
  15. Grinnell F 1992 Wound repair, keratinocyte activation and integrin modulation Journal of Cell Science 101 1 5 1569118
  16. Hsu YC Li L Fuchs E 2014 Emerging interactions between skin stem cells and their niches Nat Med 20 847 856 25100530 PMC4358898
  17. Hudson LG Newkirk KM Chandler HL Choi C Fossey SL Parent AE Kusewitt DF 2009 Cutaneous wound reepithelialization is compromised in mice lacking functional Slug (Snai2) J Dermatol Sci 56 19 26 19643582 PMC3612935
  18. Ito M Yang Z Andl T Cui C Kim N Millar SE Cotsarelis G 2007 Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding Nature 447 316 320 17507982
  19. Jiang R Lan Y Norton C Sundberg J Gridley T 1998 The slug gene is not essential for mesoderm or neural crest development in mice Developmental Biology 198 227 285 9659933
  20. Kuwahara M Hatoko M Tada H Tanaka A 2001 E-cadherin expression in wound healing of mouse skin J Cutan Pathol 28 191 199 11426826
  21. Le M Naridze R Morrison J Biggs LC Rhea L Schutte BC Kaartinen V Dunnwald M 2012 Transforming growth factor Beta 3 is required for excisional wound repair in vivo PLoS One 7 e48040 23110169 PMC3482237
  22. Lee B Villarreal-Ponce A Fallahi M Ovadia J Sun P Yu QC Ito S Sinha S Nie Q Dai X 2014 Transcriptional mechanisms link epithelial plasticity to adhesion and differentiation of epidermal progenitor cells Dev Cell 29 47 58 24735878 PMC4153751
  23. Liang X Bhattacharya S Bajaj G Guha G Wang Z Jang HS Leid M Indra AK Ganguli-Indra G 2012 Delayed cutaneous wound healing and aberrant expression of hair follicle stem cell markers in mice selectively lacking Ctip2 in epidermis PLoS One 7 e29999 22383956 PMC3283611
  24. Lim J Thiery JP 2012 Epithelial-mesenchymal transitions: insights from development Development 139 3471 3486 22949611
  25. Losick VP Fox DT Spradling AC 2013 Polyploidization and cell fusion contribute to wound healing in the adult Drosophila epithelium Curr Biol 23 2224 2232 24184101 PMC3898104
  26. Mani SA Guo W Liao MJ Eaton EN Ayyanan A Zhou AY Brooks M Reinhard F Zhang CC Shipitsin M Campbell LL Polyak K Brisken C Yang J Weinberg RA 2008 The epithelial-mesenchymal transition generates cells with properties of stem cells Cell 133 704 715 18485877 PMC2728032
  27. Martin P Lewis J 1992 Actin cables and epidermal movement in embryonic wound healing Nature 360 179 183 1436096
  28. McCluskey J Martin P 1995 Analysis of the tissue movements of embryonic wound healing–Dil studies in the limb bud stage mouse embryo Dev Biol 170 102 114 7601301
  29. Miao Q Ku AT Nishino Y Howard JM Rao AS Shaver TM Garcia GE Le DN Karlin KL Westbrook TF Poli V Nguyen H 2014 Tcf3 promotes cell migration and wound repair through regulation of lipocalin 2 Nat Commun 5 4088 24909826 PMC4052366
  30. Mitchison T Cramer L 1993 Actin-based cell motility and cell locomotion Cell 84 371 379 8608590
  31. Mustoe T Pierce G Thomason A Gramates P Sporn M Deuel T 1987 Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta Science 237 1333 1336 2442813
  32. Nieto MA 2002 The snail superfamily of zinc-finger transcription factors Nat Rev Mol Cell Biol 3 155 166 11994736
  33. Nieto MA Huang RY Jackson RA Thiery JP 2016 Emt: 2016 Cell 166 21 45 27368099
  34. Nieto MA Sargent M Wilkinson D Cooke J 1994 Control of cell behavior during vertebrate development by Slug, a zinc finger gene Science 264 835 839 7513443
  35. Nunan R Campbell J Mori R Pitulescu ME Jiang WG Harding KG Adams RH Nobes CD Martin P 2015 Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization Cell Rep 13 1380 1395 26549443 PMC4660216
  36. Odland G Ross R 1968 Human wound repair J Cell Biol 39 135 151 5678445 PMC2107509
  37. Park S Gonzalez DG Gurirao B Boucher JD Cockburn K Marsh ED Mesa KR Brown S Rompolas P Haberman AM Bellaiche Y Greco V 2017 Tissue-scale coordination of cellular behavior promotes epidermal wound repair in live mice Nat Cell Biol 19 155 164 28248302 PMC5581297
  38. Plikus MV Gay DL Treffeisen E Wang A Supapannachart RJ Cotsarelis G 2012 Epithelial stem cells and implications for wound repair Semin Cell Dev Biol 23 946 953 23085626 PMC3518754
  39. Plikus MV Guerrero-Juarez CF Ito M Li YR Dedhia PH Zheng Y Shao M Gay DL Ramos R Hsi T-C Oh JW Wang X Ramirez A Konopelski SE Elzein A Wang A Supapannachart RJ Lee H-L Lim CH Nace A Guo A Treffeisen E Andl T Ramirez RN Murad R Offermanns S Metzger D Chambon P Widgerow AD Tuan T-L Mortazavi A Gupta RK Hamilton BA Millar SE Seale P Pear WS Lazar MA Cotsarelis G 2017 Regeneration of fat cells from myofibroblasts during wound healing Science 355 748 752 28059714 PMC5464786
  40. Razzell W Wood W Martin P 2011 Swatting flies: modelling wound healing and inflammation in Drosophila Dis Model Mech 4 569 574 21810906 PMC3180219
  41. Richardson R Slanchev K Kraus C Knyphausen P Eming S Hammerschmidt M 2013 Adult zebrafish as a model system for cutaneous wound-healing research J Invest Dermatol 133 1655 1665 23325040 PMC3644348
  42. Savagner P Yamada K Thiery JP 1997 The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition J Cell Biol 137 1403 1419 9182671 PMC2132541
  43. Scheel C Eaton EN Li SH Chaffer CL Reinhardt F Kah KJ Bell G Guo W Rubin J Richardson AL Weinberg RA 2011 Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast Cell 145 926 940 21663795 PMC3930331
  44. Shaw TJ Martin P 2009 Wound repair at a glance J Cell Sci 122 3209 3213 19726630 PMC2736861
  45. Shirley SH Hudson LG He J Kusewitt DF 2010 The skinny on Slug Mol Carcinog 49 851 861 20721976 PMC3632330
  46. Stone RC Pastar I Ojeh N Chen V Liu S Garzon KI Tomic-Canic M 2016 Epithelial-mesenchymal transition in tissue repair and fibrosis Cell Tissue Res 365 495 506 27461257 PMC5011038
  47. Terao M Ishikawa A Nakahara S Kimura A Kato A Moriwaki K Kamada Y Murota H Taniguchi N Katayama I Miyoshi E 2011 Enhanced epithelial-mesenchymal transition-like phenotype in N-acetylglucosaminyltransferase V transgenic mouse skin promotes wound healing J Biol Chem 286 28303 28311 21697088 PMC3151074
  48. Thiery JP Acloque H Huang RY Nieto MA 2009 Epithelial-mesenchymal transitions in development and disease Cell 139 871 890 19945376
  49. Thomason HA Cooper NH Ansell DM Chiu M Merrit AJ Hardman MJ Garrod DR 2012 Direct evidence that PKCalpha positively regulates wound re-epithelialization: correlation with changes in desmosomal adhesiveness J Pathol 227 346 356 22407785
  50. Yan C Grimm WA Garner WL Qin L Travis T Tan N Han YP 2010 Epithelial to mesenchymal transition in human skin wound healing is induced by tumor necrosis factor-alpha through bone morphogenic protein-2 Am J Pathol 176 2247 2258 20304956 PMC2861090

Cited by

Sorted by citations

Authors
Haensel, D., & Dai, X.
Affiliations
University of California, Irvine (US)
Corresponding author
Dai, Xing
ORCID
Venue
Developmental Dynamics
Publisher
Wiley
Published
2017-09-05
Volume
247
Issue
3
Pages
473-480
ISSN
  • 1058-8388 (ISSN-L)
  • 1097-0177
DOI
10.1002/dvdy.24561
PMC
PMC5809211
OpenAlex
W2742275673
Cited by
232
References
3
Citations by year
2026: 18 · 2025: 21 · 2024: 41 · 2023: 30 · 2022: 25 · 2021: 34 · 2020: 35 · 2019: 15 · 2018: 11 · 2017: 2
FWCI
2.35
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Developmental Dynamics (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
NIH (R01‐AR47320, R01‐AR068074, R56‐AR064532)
Topics
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
epithelial-mesenchymal transition, skin wound healing, re-epithelialization, keratinocyte migration, keratinocyte proliferation, skin barrier function, epidermal regeneration
MeSH terms
Animals, Epidermis, Humans, Skin Physiological Phenomena, Wound Healing, Epithelial-Mesenchymal Transition, Re-Epithelialization

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review