Abstract
Introduction: Loss of skin integrity due to a wound or disease can lead to severe disability or even life threat. The highly expressed microRNAs in the skin are of great significance for skin development. The purpose of the investigation was to explore the effect and mechanism of miR-211 on inflammation, oxidative stress, and migration in keratinocytes. Methods: The HaCaT keratinocytes were treated with hydrogen peroxide (H2O2) to establish a wound-healing model. The expression of miR-211 was examined by quantitative real-time PCR. The cell function was reflected in proliferative ability, migration, apoptosis, and inflammation, which were evaluated using the Cell Counting Kit-8 (CCK-8) assay, transwell test, flow cytometry technique, and enzyme-linked immunosorbent assay (ELISA). The target of miR-211 was verified by luciferase luminescence measurements. Results: H2O2 inhibited HaCaT cell proliferation, migration, and promoted cell apoptosis, accompanied with the downregulation of miR-211. H2O2 led to inflammatory response and oxidative damage to HaCaT. miR-211 promoted proliferation and migration but improved cell apoptosis of HaCaT. The role of H2O2 on inflammatory response and oxidative stress was alleviated by miR-211. SRY-box transcription factor 11 (SOX11) was a targeted mediator of miR-211. SOX11 reversed the influence of miR-211 on cell proliferation, migration, apoptosis, inflammatory response, and oxidative stress. Conclusion: miR-211 regulated the proliferation, migration, apoptosis, inflammation, and oxidative stress of keratinocytes by mediating SOX11, thus participating in cutaneous wound healing.
Journal Section:
Research Article
References
1.
Kuan
CM
, Liang
CH
, Chuang
WH
, Lin
TY
, Hsu
PK
. Ameliorating effect of crassocephalum rabens (asteraceae) extract on skin aging: a randomized, parallel, double-blind, and placebo-controlled study
. Nutrients
. 2022
;14
(13
):2655
. 2.
Tavakoli
S
, Kisiel
MA
, Biedermann
T
, Klar
AS
. Immunomodulation of skin repair: cell-based therapeutic strategies for skin replacement (A comprehensive review)
. Biomedicines
. 2022
;10
(1
):118
. 3.
Xu
J
, Zheng
S
, Hu
X
, Li
L
, Li
W
, Parungao
R
, et al. Advances in the research of bioinks based on natural collagen, polysaccharide and their derivatives for skin 3D bioprinting
. Polym
. 2020
;12
(6
):1237
. 4.
Song
Y
, Wu
C
, Zhang
X
, Bian
W
, Liu
N
, Yin
S
, et al. A short peptide potentially promotes the healing of skin wound
. Biosci Rep
. 2019
;39
(3
). 5.
Kowalska
G
, Rosicka-Kaczmarek
J
, Miśkiewicz
K
, Zakłos-Szyda
M
, Rohn
S
, Kanzler
C
, et al. Arabinoxylan-based microcapsules being loaded with bee products as bioactive food components are able to modulate the cell migration and inflammatory response-in vitro study
. Nutrients
. 2022
;14
(12
):2529
. 6.
He
CP
, Jiang
XC
, Chen
C
, Zhang
HB
, Cao
WD
, Wu
Q
, et al. The function of lncRNAs in the pathogenesis of osteoarthritis
. Bone Jt Res
. 2021
;10
(2
):122
–33
. 7.
Čoma
M
, Fröhlichová
L
, Urban
L
, Zajíček
R
, Urban
T
, Szabo
P
, et al. Molecular changes underlying hypertrophic scarring following burns involve specific deregulations at all wound healing stages (inflammation, proliferation and maturation)
. Int J Mol Sci
. 2021
;22
(2
):897
. 8.
Heuer
A
, Stiel
C
, Elrod
J
, Konigs
I
, Vincent
D
, Schlegel
P
, et al. Therapeutic targeting of neutrophil extracellular traps improves primary and secondary intention wound healing in mice
. Front Immunol
. 2021
;12
:614347
. 9.
Bojanic
C
, To
K
, Hatoum
A
, Shea
J
, Seah
KTM
, Khan
W
, et al. Mesenchymal stem cell therapy in hypertrophic and keloid scars
. Cell Tissue Res
. 2021
;383
(3
):915
–30
. 10.
Wang
G
, Yang
F
, Zhou
W
, Xiao
N
, Luo
M
, Tang
Z
. The initiation of oxidative stress and therapeutic strategies in wound healing
. Biomed Pharmacother
. 2023
;157
:114004
. 11.
He
YB
, Su
YY
, Rajah
GB
, Zhang
YB
, Fan
LL
, Liu
G
, et al. Trans-cranial Doppler predicts early neurologic deterioration in anterior circulation ischemic stroke after successful endovascular treatment
. Chin Med J
. 2020
;133
(14
):1655
–61
. 12.
Sonkoly
E
, Wei
T
, Pavez Loriè
E
, Suzuki
H
, Kato
M
, Törmä
H
, et al. Protein kinase C-dependent upregulation of miR-203 induces the differentiation of human keratinocytes
. J Invest Dermatol
. 2010
;130
(1
):124
–34
. 13.
Liu
G
, Li
S
, Liu
H
, Zhu
Y
, Bai
L
, Sun
H
, et al. The functions of ocu-miR-205 in regulating hair follicle development in Rex rabbits
. BMC Dev Biol
. 2020
;20
(1
):8
. 14.
Ahmed
MI
, Alam
M
, Emelianov
VU
, Poterlowicz
K
, Patel
A
, Sharov
AA
, et al. MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway
. J Cell Biol
. 2014
;207
(4
):549
–67
. 15.
Jin
F
, Li
M
, Li
X
, Zheng
Y
, Zhang
K
, Liu
X
, et al. DNMT1-mediated methylation inhibits microRNA-214-3p and promotes hair follicle stem cell differentiate into adipogenic lineages
. Stem Cell Res Ther
. 2020
;11
(1
):444
. 16.
Li
D
, Li
XI
, Wang
A
, Meisgen
F
, Pivarcsi
A
, Sonkoly
E
, et al. MicroRNA-31 promotes skin wound healing by enhancing keratinocyte proliferation and migration
. J Invest Dermatol
. 2015
;135
(6
):1676
–85
. 17.
Li
X
, Li
D
, Wikstrom
JD
, Pivarcsi
A
, Sonkoly
E
, Ståhle
M
, et al. MicroRNA-132 promotes fibroblast migration via regulating RAS p21 protein activator 1 in skin wound healing
. Sci Rep
. 2017
;7
(1
):7797
. 18.
Bi
Q
, Liu
J
, Wang
X
, Sun
F
. Downregulation of miR-27b promotes skin wound healing in a rat model of scald burn by promoting fibroblast proliferation
. Exp Ther Med
. 2020
;20
(5
):63
. 19.
Yang
C
, Luo
L
, Bai
X
, Shen
K
, Liu
K
, Wang
J
, et al. Highly-expressed micoRNA-21 in adipose derived stem cell exosomes can enhance the migration and proliferation of the HaCaT cells by increasing the MMP-9 expression through the PI3K/AKT pathway
. Arch Biochem Biophys
. 2020
;681
:108259
. 20.
Meisgen
F
, Xu
N
, Wei
T
, Janson
PC
, Obad
S
, Broom
O
, et al. MiR-21 is up-regulated in psoriasis and suppresses T cell apoptosis
. Exp Dermatol
. 2012
;21
(4
):312
–4
. 21.
Han
D
, Liu
W
, Li
G
, Liu
L
. Circ_PRKDC knockdown promotes skin wound healing by enhancing keratinocyte migration via miR-31/FBN1 axis
. J Mol Histol
. 2021
;52
(4
):681
–91
. 22.
Xu
N
, Meisgen
F
, Butler
LM
, Han
G
, Wang
XJ
, Söderberg-Nauclér
C
, et al. MicroRNA-31 is overexpressed in psoriasis and modulates inflammatory cytokine and chemokine production in keratinocytes via targeting serine/threonine kinase 40
. J Immunol
. 2013
;190
(2
):678
–88
. 23.
Sahoo
A
, Lee
B
, Boniface
K
, Seneschal
J
, Sahoo
SK
, Seki
T
, et al. MicroRNA-211 regulates oxidative phosphorylation and energy metabolism in human vitiligo
. J Invest Dermatol
. 2017
;137
(9
):1965
–74
. 24.
Tang
J
, Yang
J
, Hu
H
, Cen
Y
, Chen
J
. miR-211-5p inhibits the proliferation, migration, invasion, and induces apoptosis of human hypertrophic scar fibroblasts by regulating TGFβR2 expression
. Ann Transl Med
. 2021
;9
(10
):864
. 25.
Brahmbhatt
HD
, Gupta
R
, Gupta
A
, Rastogi
S
, Misri
R
, Mobeen
A
, et al. The long noncoding RNA MALAT1 suppresses miR-211 to confer protection from ultraviolet-mediated DNA damage in vitiligo epidermis by upregulating sirtuin 1
. Br J Dermatol
. 2021
;184
(6
):1132
–42
. 26.
Kraokaew
P
, Manohong
P
, Prasertsuksri
P
, Jattujan
P
, Niamnont
N
, Tamtin
M
, et al. Ethyl acetate extract of marine algae, halymenia durvillei, provides photoprotection against UV-exposure in L929 and HaCaT cells
. Mar Drugs
. 2022
;20
(11
):707
. 27.
He
L
, Zhu
C
, Jia
J
, Hao
XY
, Yu
XY
, Liu
XY
, et al. ADSC-Exos containing MALAT1 promotes wound healing by targeting miR-124 through activating Wnt/β-catenin pathway
. Biosci Rep
. 2020
;40
(5
). 28.
Perrault
DP
, Bramos
A
, Xu
X
, Shi
S
, Wong
AK
. Local administration of interleukin-1 receptor antagonist improves diabetic wound healing
. Ann Plast Surg
. 2018
;80
(5S Suppl 5
):S317
–21
. 29.
Bertaux-Skeirik
N
, Wunderlich
M
, Teal
E
, Chakrabarti
J
, Biesiada
J
, Mahe
M
, et al. CD44 variant isoform 9 emerges in response to injury and contributes to the regeneration of the gastric epithelium
. J Pathol
. 2017
;242
(4
):463
–75
. 30.
Yang
L
, Zheng
Z
, Zhou
Q
, Bai
X
, Fan
L
, Yang
C
, et al. miR-155 promotes cutaneous wound healing through enhanced keratinocytes migration by MMP-2
. J Mol Histol
. 2017
;48
(2
):147
–55
. 31.
Wu
P
, Cao
Y
, Zhao
R
, Wang
Y
. miR-96-5p regulates wound healing by targeting BNIP3/FAK pathway
. J Cell Biochem
. 2019
;120
(8
):12904
–11
. 32.
Chiangnoon
R
, Samee
W
, Uttayarat
P
, Jittachai
W
, Ruksiriwanich
W
, Sommano
SR
, et al. Phytochemical analysis, antioxidant, and wound healing activity of pluchea indica L. (Less) branch extract nanoparticles
. Molecules
. 2022
;27
(3
):635
. 33.
Jaurila
H
, Koivukangas
V
, Koskela
M
, Gäddnäs
F
, Salo
S
, Korvala
J
, et al. Inhibitory effects of serum from sepsis patients on epithelial cell migration in vitro: a case control study
. J Transl Med
. 2017
;15
(1
):11
. 34.
Brito
SA
, Barbosa
IS
, de Almeida
CLF
, de Medeiros
JW
, Silva Neto
JC
, Rolim
LA
, et al. Evaluation of gastroprotective and ulcer healing activities of yellow mombin juice from Spondias mombin L
. PLoS One
. 2018
;13
(11
):e0201561
. 35.
Quan
J
, Pan
X
, He
T
, Lin
C
, Lai
Y
, Chen
P
, et al. Tumor suppressor miR-211-5p is associated with cellular migration, proliferation and apoptosis in renal cell carcinoma
. Exp Ther Med
. 2018
;15
(4
):4019
–28
. 36.
Tao
F
, Tian
X
, Ruan
S
, Shen
M
, Zhang
Z
. miR-211 sponges lncRNA MALAT1 to suppress tumor growth and progression through inhibiting PHF19 in ovarian carcinoma
. FASEB j
. 2018
;32
(11
):6330
–43
. 37.
Hoff
J
, Karl
B
, Gerstmeier
J
, Beekmann
U
, Schmölz
L
, Börner
F
, et al. Controlled release of the α-tocopherol-derived metabolite α-13'-carboxychromanol from bacterial nanocellulose wound cover improves wound healing
. Nanomaterials
. 2021
;11
(8
):1939
. 38.
Yang
C
, Yang
C
, Zhang
J
, Guo
Y
, Chen
N
, Yin
B
, et al. MicroRNA-211 regulates the expression of TAB1 and inhibits the NF-κB signaling pathway in lipopolysaccharide-induced endometritis
. Int Immunopharmacol
. 2021
;96
:107668
. 39.
Tao
D
, Liu
Z
, Wang
L
, Li
C
, Zhang
R
, Ni
N
. CircPAG1 interacts with miR-211-5p to promote the E2F3 expression and inhibit the high glucose-induced cell apoptosis and oxidative stress in diabetic cataract
. Cell Cycle
. 2022
;21
(7
):708
–19
. 40.
Li
X
, Quan
P
, Si
Y
, Liu
F
, Fan
Y
, Ding
F
, et al. The microRNA-211-5p/P2RX7/ERK/GPX4 axis regulates epilepsy-associated neuronal ferroptosis and oxidative stress
. J Neuroinflammation
. 2024
;21
(1
):13
. 41.
Miao
Q
, Hill
MC
, Chen
F
, Mo
Q
, Ku
AT
, Ramos
C
, et al. SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair
. Nat Commun
. 2019
;10
(1
):4042
. 42.
Feng
JS
, Sun
JD
, Wang
XD
, Fu
CH
, Gan
LL
, Ma
R
. MicroRNA-204-5p targets SOX11 to regulate the inflammatory response in spinal cord injury
. Eur Rev Med Pharmacol Sci
. 2019
;23
(10
):4089
–96
. © 2025 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2025
You do not currently have access to this content.
