Fibroblast growth factor 2 accelerates the epithelial-mesenchymal transition in keratinocytes during wound healing process
- PMID: 33122782
- PMCID: PMC7596476
- DOI: 10.1038/s41598-020-75584-7
Fibroblast growth factor 2 accelerates the epithelial-mesenchymal transition in keratinocytes during wound healing process
Abstract
In the wound healing process, the morphology of keratinocytes at the wound edge temporarily changes to a spindle morphology, which is thought to occur due to an epithelial-mesenchymal transition (EMT). Fibroblast growth factor (FGF) 2, also called basic FGF, has the potential to accelerate wound closure by activating vascular endothelial cells and fibroblasts. We examined the effects of FGF2 on keratinocyte morphology and EMT in wounded skin. Histological examination of murine wounds treated with FGF2 revealed that wound edge keratinocytes formed thickened and multilayered epithelia. In addition, we detected wound edge keratinocytes migrating individually toward the wound center. These migrating keratinocytes exhibited not only spindle morphology but also down-regulated E-cadherin and up-regulated vimentin expression, which is characteristic of EMT. In FGF2-treated wounds, a PCR array revealed the upregulation of genes related to EMT, including transforming growth factor (TGF) signaling. Further, FGF2-treated wound edge keratinocytes expressed EMT-associated transcription factors, including Snai2, and showed translocation of β-catenin from the cell membrane to the cytoplasm/nucleus. However, in vitro examination of keratinocytes revealed that FGF2 alone did not activate EMT in keratinocytes, but that FGF2 might promote EMT in combination with TGFβ1. These findings suggest that FGF2 treatment of wounds could promote keratinocyte EMT, accelerating wound closure.
Conflict of interest statement
The authors declare no competing interests.
Figures







Similar articles
-
Electric field-induced suppression of PTEN drives epithelial-to-mesenchymal transition via mTORC1 activation.J Dermatol Sci. 2017 Feb;85(2):96-105. doi: 10.1016/j.jdermsci.2016.11.007. Epub 2016 Nov 18. J Dermatol Sci. 2017. PMID: 27919618
-
Vimentin coordinates fibroblast proliferation and keratinocyte differentiation in wound healing via TGF-β-Slug signaling.Proc Natl Acad Sci U S A. 2016 Jul 26;113(30):E4320-7. doi: 10.1073/pnas.1519197113. Epub 2016 Jul 8. Proc Natl Acad Sci U S A. 2016. PMID: 27466403 Free PMC article.
-
Fibroblast Growth Factor 2 Augments Transforming Growth Factor Beta 1 Induced Epithelial-mesenchymal Transition in Lung Cell Culture Model.Iran J Allergy Asthma Immunol. 2020 Aug 25;19(4):348-361. doi: 10.18502/ijaai.v19i4.4110. Iran J Allergy Asthma Immunol. 2020. PMID: 33463102 Free PMC article.
-
Epithelial-mesenchymal transition, TGF-β, and osteopontin in wound healing and tissue remodeling after injury.J Burn Care Res. 2012 May-Jun;33(3):311-8. doi: 10.1097/BCR.0b013e318240541e. J Burn Care Res. 2012. PMID: 22561306 Free PMC article. Review.
-
Transforming growth factor-beta and wound healing.Perspect Vasc Surg Endovasc Ther. 2006 Mar;18(1):55-62. doi: 10.1177/153100350601800123. Perspect Vasc Surg Endovasc Ther. 2006. PMID: 16628336 Review.
Cited by
-
Effects of Angiogenic Factors on the Epithelial-to-Mesenchymal Transition and Their Impact on the Onset and Progression of Oral Squamous Cell Carcinoma: An Overview.Cells. 2024 Jul 31;13(15):1294. doi: 10.3390/cells13151294. Cells. 2024. PMID: 39120324 Free PMC article. Review.
-
Investigation of the potential therapeutic effect of cationic lipoplex mediated fibroblast growth factor-2 encoding plasmid DNA delivery on wound healing.Daru. 2021 Dec;29(2):329-340. doi: 10.1007/s40199-021-00410-y. Epub 2021 Sep 7. Daru. 2021. PMID: 34491567 Free PMC article.
-
The relationship between salivary Fibroblast Growth Factor-2 and cortisol reactivity and psychological outcomes prior to and during the COVID-19 pandemic.J Affect Disord Rep. 2023 Jul;13:100606. doi: 10.1016/j.jadr.2023.100606. Epub 2023 Jun 7. J Affect Disord Rep. 2023. PMID: 37304226 Free PMC article.
-
ROS-scavenging materials for skin wound healing: advancements and applications.Front Bioeng Biotechnol. 2023 Dec 12;11:1304835. doi: 10.3389/fbioe.2023.1304835. eCollection 2023. Front Bioeng Biotechnol. 2023. PMID: 38149175 Free PMC article. Review.
-
Signaling Pathways Associated with Chronic Wound Progression: A Systems Biology Approach.Antioxidants (Basel). 2022 Jul 31;11(8):1506. doi: 10.3390/antiox11081506. Antioxidants (Basel). 2022. PMID: 36009225 Free PMC article.
References
-
- Grinnell F. Wound repair, keratinocyte activation and integrin modulation. J. Cell Sci. 1992;101(Pt 1):1–5. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials