Abstract
Background
Wound re-epithelialization is considered as an extremely important link in the complete reconstruction of the epidermal barrier. The present study is aimed to determine the association between transforming growth factor β (TGF-β) and re-epithelialization.
Objective
It was aimed to explore the possible molecular mechanism of TGF-β mediated re-epithelialization.
Results
NEAT1 was upregulated in TGF-β1-treated HaCaT cells and promoted cell proliferation. NEAT1 overexpression enhanced the wound healing and upregulated MMP-2 and MMP-9 in TGF-β1-treated HaCaT cells. Mechanically, TGF-β1 down-regulated miR-26a-5p through targeting NEAT1 in HaCaT cells. Furthermore, NEAT1/miR-26a-5p axis regulated the expression of LGR4 in HaCaT cells. Finally, the results showed that NEAT1/miR-26a-5p/LGR4 axis was involved in TGF-β1-mediated re-epithelialization.
Conclusion
NEAT1/miR-26a-5p/LGR4 network is an important participant in TGF-β1-mediated keratinocyte proliferation and migration, which provides a novel perspective for understanding the cellular behavior and related molecular events in re-epithelialization.
Similar content being viewed by others
References
Abdel-Lateff A et al (2021) Euryops arabicus promotes healing of excised wounds in rat skin: Emphasis on its collagen-enhancing, antioxidant, and anti-inflammatory activities. Oxid Med Cell Longev. https://doi.org/10.1155/2021/8891445
Anantharaman A et al (2016) Paraspeckles modulate the intranuclear distribution of paraspeckle-associated Ctn RNA. Sci Rep 6:1–12
Barker N, Tan S, Clevers H (2013) Lgr proteins in epithelial stem cell biology. Development 140:2484–2494
Berman B, Maderal A, Raphael B (2017) Keloids and hypertrophic scars: pathophysiology, classification, and treatment. Dermatol Surg 43:S3–S18
Dekoninck S, Blanpain C (2019) Stem cell dynamics, migration and plasticity during wound healing. Nat Cell Biol 21:18–24
Fan J-T et al (2021) Exosomal lncRNA NEAT1 from cancer-associated fibroblasts facilitates endometrial cancer progression via miR-26a/b-5p-mediated STAT3/YKL-40 signaling pathway. Neoplasia 23:692–703
Gill SE, Parks WC (2008) Metalloproteinases and their inhibitors: regulators of wound healing. Int J Biochem Cell Biol 40:1334–1347
He L et al (2020) ADSC-Exos containing MALAT1 promotes wound healing by targeting miR-124 through activating Wnt/β-catenin pathway. Biosci Rep. https://doi.org/10.1042/BSR20192549
Hu M et al (2020) Novel long noncoding RNA lnc-URIDS delays diabetic wound healing by targeting Plod1. Diabetes 69:2144–2156
Jiang Z et al (2020) MicroRNA-26a inhibits wound healing through decreased keratinocytes migration by regulating ITGA5 through PI3K/AKT signaling pathway. Biosci Rep. https://doi.org/10.1042/BSR20201361
Kim KK, Sheppard D, Chapman HA (2018) TGF-β1 signaling and tissue fibrosis. Cold Spring Harb Perspect Biol 10:a022293
Li P et al (2020) Aloin promotes cell apoptosis by targeting HMGB1-TLR4-ERK axis in human melanoma cells. EXCLI J 19:641
Liarte S, Bernabé-García Á, Nicolás FJ (2020) Role of TGF-β in skin chronic wounds: a keratinocyte perspective. Cells 9:306
Liu Y, Liu D (2016) Long non-coding RNA and wound healing. Zhonghua Shao Shang za zhi Zhonghua Shaoshang Zazhi Chin J Burns 32:735–739
Liu J et al (2020) The interplay between ATF2 and NEAT1 contributes to lung adenocarcinoma progression. Cancer Cell Int 20:1–13
Luckett-Chastain LR et al (2017) Interleukin (IL)-6 modulates transforming growth factor-β receptor I and II (TGF-β RI and II) function in epidermal keratinocytes. Exp Dermatol 26:697–704
Martin P, Nunan R (2015) Cellular and molecular mechanisms of repair in acute and chronic wound healing. Br J Dermatol 173:370–378
Meng Z et al (2018) miRNA delivery for skin wound healing. Adv Drug Deliv Rev 129:308–318
Muscella A, Vetrugno C, Cossa LG, Marsigliante S (2020) TGF-β1 activates RSC96 Schwann cells migration and invasion through MMP-2 and MMP-9 activities. J Neurochem 153:525–538
Raffetto JD et al (2020) Why venous leg ulcers have difficulty healing: overview on pathophysiology, clinical consequences, and treatment. J Clin Med 10:29
Riedel U et al (2020) Wound treatment in diabetes patients and diabetic foot ulcers. Der Hautarzt; Zeitschrift fur Dermatologie. Venerol Und Verwandte Gebiete 71:835–842
Shen X, Zhao W, Zhang Y, Liang B (2020) Long non-coding RNA-NEAT1 promotes cell migration and invasion via regulating miR-124/NF-κB pathway in cervical cancer. Onco Targets Ther 13:3265
Shi C et al (2021) NEAT1 promotes the repair of abdominal aortic aneurysms of endothelial progenitor cells via regulating miR-204-5p/Ang-1. Am J Transl Res 13:2111
Sorg H et al (2017) Skin wound healing: an update on the current knowledge and concepts. Eur Surg Res 58:81–94
Sun P et al (2019) Loss of Lgr4 inhibits differentiation, migration and apoptosis, and promotes proliferation in bone mesenchymal stem cells. J Cell Physiol 234:10855–10867
Wang AW, Hoyt MA (2018) Benefit finding and diurnal cortisol after prostate cancer: the mediating role of positive affect. Psychooncology 27:1200–1205
Wang L, Zhu H (2018) Long non-coding nuclear paraspeckle assembly transcript 1 acts as prognosis biomarker and increases cell growth and invasion in cervical cancer by sequestering microRNA-101. Mol Med Rep 17:2771–2777
Wang F et al (2020) Akermanite bioceramic enhances wound healing with accelerated reepithelialization by promoting proliferation, migration, and stemness of epidermal cells. Wound Repair Regen 28:16–25
Wang L et al (2021) Long non-coding RNA NEAT1 functions as a competing endogenous RNA to regulate S100A9 expression by sponging miR-196a-5p in rosacea. J Dermatol Sci 102:58–67
Wang X-J, Han G, Owens P, Siddiqui Y, Li AG (2006) Role of TGFβ-mediated inflammation in cutaneous wound healing. J Invest Dermatol Symposium Proceedings, Elsevier 2006:112–117
Wu J et al (2020) MicroRNA-34 family enhances wound inflammation by targeting LGR4. J Investig Dermatol 140(465–476):e411
Yang L, Wang M, He P (2020) LncRNA NEAT1 promotes the progression of gastric cancer through modifying the miR-1224-5p/RSF1 signaling axis. Cancer Manag Res 12:11845
Yang J et al (2021) NEAT1 knockdown inhibits keloid fibroblast progression by miR-196b-5p/FGF2 axis. J Surg Res 259:261–270
Yu X et al (2017) NEAT 1: a novel cancer-related long non-coding RNA. Cell Prolif 50:e12329
Zhao Y-X et al (2017) Role of homeodomain-interacting protein kinase 2 in the pathogenesis of tissue fibrosis in keloid-derived keratinocytes. Ann Plast Surg 79:546–551
Acknowledgements
Not applicable.
Funding
Not applicable.
Author information
Authors and Affiliations
Contributions
LZ, RT and KW designed the study, supervised the data collection, analyzed the data, interpreted the data, prepared the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
Author Lan Zhang declares that he/she has no conflict of interest; author Rong Tian declares that he/she has no conflict of interest; author Kui Wang declares that he/she has no conflict of interest.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Zhang, L., Tian, R. & Wang, K. NEAT1 promotes keratinocyte migration and proliferation during wound healing by regulating miR-26a-5p/LGR4 axis. Mol. Cell. Toxicol. 19, 473–481 (2023). https://doi.org/10.1007/s13273-022-00275-5
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13273-022-00275-5