MiR-125a-3p alleviates hyperproliferation of keratinocytes
and psoriasis-like inflammation by targeting TLR4/NF-κB
pathway

Zhao Jin; Qinsi Huang; Jing Peng; Zhong Liu; Rongyi Hu; Juan Wu; Fei Wang

doi:10.5114/ada.2023.129155

eISSN: 2299-0046
ISSN: 1642-395X

Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii

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abstract:

Original paper

MiR-125a-3p alleviates hyperproliferation of keratinocytes and psoriasis-like inflammation by targeting TLR4/NF-κB pathway

Zhao Jin

¹

,

Qinsi Huang

¹

,

Jing Peng

¹

,

Zhong Liu

¹

,

Rongyi Hu

¹

,

Juan Wu

¹

,

Fei Wang

²

Department of Dermatology, Wuhan No. 1 Hospital, Wuhan, Hubei, China
Department of Chinese Medicine, Wuhan No. 1 Hospital, Wuhan, Hubei, China

Adv Dermatol Allergol 2023; XL (3): 447–461

DOI: https://doi.org/10.5114/ada.2023.129155

Online publish date: 2023/07/16

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AMA

Jin Z, Huang Q, Peng J, et al. MiR-125a-3p alleviates hyperproliferation of keratinocytes
and psoriasis-like inflammation by targeting TLR4/NF-κB
pathway. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2023;40(3):447-461. doi:10.5114/ada.2023.129155.

APA

Jin, Z., Huang, Q., Peng, J., Liu, Z., Hu, R.,  & Wu, J. et al. (2023). MiR-125a-3p alleviates hyperproliferation of keratinocytes
and psoriasis-like inflammation by targeting TLR4/NF-κB
pathway. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 40(3), 447-461. https://doi.org/10.5114/ada.2023.129155

Chicago

Jin, Zhao, Qinsi Huang, Jing Peng, Zhong Liu, Rongyi Hu, Juan Wu,  and Fei Wang. 2023. "MiR-125a-3p alleviates hyperproliferation of keratinocytes
and psoriasis-like inflammation by targeting TLR4/NF-κB
pathway". Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii 40 (3): 447-461. doi:10.5114/ada.2023.129155.

Harvard

Jin, Z., Huang, Q., Peng, J., Liu, Z., Hu, R., Wu, J.,  and Wang, F. (2023). MiR-125a-3p alleviates hyperproliferation of keratinocytes
and psoriasis-like inflammation by targeting TLR4/NF-κB
pathway. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 40(3), pp.447-461. https://doi.org/10.5114/ada.2023.129155

MLA

Jin, Zhao et al. "MiR-125a-3p alleviates hyperproliferation of keratinocytes
and psoriasis-like inflammation by targeting TLR4/NF-κB
pathway." Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, vol. 40, no. 3, 2023, pp. 447-461. doi:10.5114/ada.2023.129155.

Vancouver

Jin Z, Huang Q, Peng J, Liu Z, Hu R, Wu J et al. MiR-125a-3p alleviates hyperproliferation of keratinocytes
and psoriasis-like inflammation by targeting TLR4/NF-κB
pathway. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2023;40(3):447-461. doi:10.5114/ada.2023.129155.

Introduction:
Psoriasis is a chronic auto-inflammatory dermatosis characterized by hyperproliferation of keratinocytes. Emerging evidence has validated the dysregulated expression of microRNAs (miRNAs/miRs) in psoriasis patients.

Aim:
To probe into the role and precise mechanism of miR-125a-3p in HaCaT cells and imiquimod (IMQ)-stimulated psoriasis-like mice.

Material and methods:
In M5-treated HaCaT cells and IMQ-stimulated psoriasis-like mice, real-time quantitative polymerase chain reaction and western blot analysis were performed for detecting gene expression. Hematoxylin and eosin staining was used to evaluate pathological morphology of IMQ-induced psoriasis skin. The proliferation of keratinocytes was assessed using Cell Counting Kit-8 assay and Ki67 positive staining. The combination between miR-125a-3p and Toll-like receptor 4 (TLR4) was confirmed by luciferase reporter assay.

Results:
Our studyshowed reduced miR-125a-3p expression in psoriasis patients, psoriasis-like inflammatory cell models, and IMQ-generated psoriasis-like mouse models. MiR-125a-3p repressed the activity of keratinocytes in vitro by suppressing cell proliferation, inhibiting the production of psoriasis-related genes and inflammatory genes, and inactivating the NF-κB and interleukin (IL)-1β pathways. Notably, the psoriasis-like inflammation was repressed by intradermal injection of agomiR-125a-3p in psoriatic mouse models in vivo. Mechanically, miR-125a-3p targeted and negatively regulated TLR4. Furthermore, the elevated expression of TLR4 reversed the influences of miR-125a-3p mimics on HaCaT cells.

Conclusions:
Upregulation of miR-125a-3p protects keratinocytes against hyperproliferation and inflammatory damage by inhibiting TLR4, suggesting that the miR-125a-3p/TLR4 axis might become a novel target for the prevention of psoriasis.

keywords:

MiR-125a-3p alleviates hyperproliferation of keratinocytes and psoriasis-like inflammation by targeting TLR4/NF-κB pathway

Zhao Jin 1 , Qinsi Huang 1 , Jing Peng 1 , Zhong Liu 1 , Rongyi Hu 1 , Juan Wu 1 , Fei Wang 2

miR-125a-3p, psoriasis, hyperproliferation, inflammation, Toll-like receptor 4

Zhao Jin

¹

,

Qinsi Huang

¹

,

Jing Peng

¹

,

Zhong Liu

¹

,

Rongyi Hu

¹

,

Juan Wu

¹

,

Fei Wang

²