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Volume 6 Issue 2
Apr.  2026
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Article Navigation >  Frigid Zone Medicine  > 2026  >  6(2): 117-127
Meng Tong, Guangyu Yang, Yizhou Hu, Tao Li, Yuge Gao, Yuzhen Li. LncRNA MIR4435-2HG promotes psoriatic inflammation via activation of PDGFRB-positive skin mesenchymal cells[J]. Frigid Zone Medicine, 2026, 6(2): 117-127. doi: 10.1515/fzm-2026-0012
Citation: Meng Tong, Guangyu Yang, Yizhou Hu, Tao Li, Yuge Gao, Yuzhen Li. LncRNA MIR4435-2HG promotes psoriatic inflammation via activation of PDGFRB-positive skin mesenchymal cells[J]. Frigid Zone Medicine, 2026, 6(2): 117-127. doi: 10.1515/fzm-2026-0012
shu

LncRNA MIR4435-2HG promotes psoriatic inflammation via activation of PDGFRB-positive skin mesenchymal cells

doi: 10.1515/fzm-2026-0012
  • 1.

    Department of Dermatology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China

  • 2.

    Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17165, Sweden

  • 3.

    Department of Chief Physician, Daqing Oilfield General Hospital, Daqing 163000, China

Funds:

The authors declare financial support was received for the research, authorship, and/or publication of this article 

the National Natural Science Foundation of China 81972925

Heilongjiang Postdoctoral Research Fund LBH-Z21174

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    Abstract
  •   Background  Psoriasis is a chronic inflammatory skin disease influenced by genetic, immune, and environmental factors. Notably, its prevalence is significantly higher in colder regions, and cold climates are known to exacerbate disease symptoms. This study aimed to investigate the role of the long non-coding RNA MIR4435-2HG in regulating inflammation and cytokine production in psoriatic skin.  Methods  Single-cell RNA sequencing identified MIR4435-2HG expression in PDGFRB-positive mesenchymal cell subsets in psoriatic skin. Functional assays were performed to evaluate its effects on inflammatory cytokine expression in mesenchymal cells activated by TNF-α. An imiquimod-induced psoriasis mouse model was used to assess the effects of MIR4435-2HG knockdown in vivo.  Results  MIR4435-2HG was found to upregulate IL-6, CXCL8, and IL-17B expression in TNF-α-activated mesenchymal cells. Knockdown of MIR4435-2HG in the mouse model significantly reduced skin inflammation, epidermal hyperplasia, and psoriasis-associated cytokine expression.  Conclusion  MIR4435-2HG plays a critical role in regulating inflammation through mesenchymal cell activation, offering a potential therapeutic target for reducing psoriasis severity, especially in cold climates.

     

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    • References(45)
  • [1]
    Parisi R, Iskandar I Y K, Kontopantelis E, et al. National, regional, and worldwide epidemiology of psoriasis: Systematic analysis and modelling study. BMJ, 2020; 369: m1590.
    [2]
    Jensen K K, Serup J, Alsing K K. Psoriasis and seasonal variation: A systematic review on reports from Northern and Central Europe-Little overall variation but distinctive subsets with improvement in summer or wintertime. Skin Res Technol, 2022; 28(1): 180-186. doi: 10.1111/srt.13102
    [3]
    Woolf R, Nussbaumer O, Hayday A. Potential for innate-like responsiveness of resident T cells in human skin: a new perspective on tissue immune-surveillance. The Lancet, 2016; 387: S108. doi: 10.1016/S0140-6736(16)00495-5
    [4]
    Li Z, Cao T, Li Q, et al. Cross-disease characterization of fibroblast heterogeneities and their pathogenic roles in skin inflammation. Clin Immunol, 2023; 255: 109742. doi: 10.1016/j.clim.2023.109742
    [5]
    Castillo R L, Sidhu I, Dolgalev I, et al. Spatial transcriptomics stratifies psoriatic disease severity by emergent cellular ecosystems. Sci Immunol, 2023; 8(84): eabq7991. doi: 10.1126/sciimmunol.abq7991
    [6]
    Guo D, Li X, Wang J, et al. Single-cell RNA-seq reveals keratinocyte and fibroblast heterogeneity and their crosstalk via epithelialmesenchymal transition in psoriasis. Cell Death Dis, 2024; 15(3): 207. doi: 10.1038/s41419-024-06583-z
    [7]
    Gupta R, Ahn R, Lai K, et al. Landscape of long noncoding RNAs in psoriatic and healthy skin. J Invest Dermatol, 2016; 136(3): 603-609. doi: 10.1016/j.jid.2015.12.009
    [8]
    Lin J, Li X, Zhang F, et al. Transcriptome wide analysis of long non-coding RNA-associated ceRNA regulatory circuits in psoriasis. J Cell Mol Med, 2021; 25(14): 6925-6935. doi: 10.1111/jcmm.16703
    [9]
    Jiang Z, Feng T, Lu Z, et al. PDGFRb(+) mesenchymal cells, but not NG2(+) mural cells, contribute to cardiac fat. Cell Rep, 2021; 34(5): 108697. doi: 10.1016/j.celrep.2021.108697
    [10]
    Zhang M, Yu X, Zhang Q, et al. MIR4435-2HG: A newly proposed lncRNA in human cancer. Biomed Pharmacother, 2022; 150: 112971. doi: 10.1016/j.biopha.2022.112971
    [11]
    Cai S, Fan C, Xie L, et al. Single-cell RNA sequencing reveals the potential mechanism of heterogeneity of immunomodulatory properties of foreskin and umbilical cord mesenchymal stromal cells. Cell Biosci, 2022; 12(1): 115. doi: 10.1186/s13578-022-00848-w
    [12]
    Committee on Psoriasis, Chinese Society of Dermatology. Guideline for the diagnosis and treatment of psoriasis in China (2023 edition). Chinese Journal of Dermatology, 2023; 56(7): 573-625.
    [13]
    He Y, Huang M, Wang Y, et al. Inhibition of CTSC contributes to psoriasis inflammation and keratinocyte hyperproliferation by NF-κB signaling pathway. Int Immunopharmacol, 2025; 157: 114808. doi: 10.1016/j.intimp.2025.114808
    [14]
    Kulig P, Brazauskas P, Suffiotti M, et al. Efficacy of IDOR-1117-2520, a novel, orally available CCR6 antagonist in preclinical models of skin dermatitis. Br J Pharmacol, 2025; 182(15): 3452-3475. doi: 10.1111/bph.70025
    [15]
    Gao Y, Yao X, Zhai Y, et al. Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis conducted by skin resident cells. Cell Death Dis, 2021; 12(5): 450. doi: 10.1038/s41419-021-03724-6
    [16]
    Kirkwood P M, Gibson D A, Shaw I, et al. Single-cell RNA sequencing and lineage tracing confirm mesenchyme to epithelial transformation (MET) contributes to repair of the endometrium at menstruation. Elife, 2022; 11: e77663. doi: 10.7554/eLife.77663
    [17]
    Yoshida N, Yamamoto S, Hamashima T, et al. Dysregulation of Amphiregulin stimulates the pathogenesis of cystic lymphangioma. Proc Natl Acad Sci U S A, 2021; 118(19): e2019580118. doi: 10.1073/pnas.2019580118
    [18]
    Li Y, He Y, Yang F, et al. Gasdermin E-mediated keratinocyte pyroptosis participates in the pathogenesis of psoriasis by promoting skin inflammation. Br J Dermatol, 2024; 191(3): 385-396. doi: 10.1093/bjd/ljae179
    [19]
    Zhang S, Zhang J, Yu J, et al. Hyperforin ameliorates imiquimod-induced psoriasis-like murine skin inflammation by modulating IL-17A-producing γδ T cells. Front Immunol, 2021; 12: 635076. doi: 10.3389/fimmu.2021.635076
    [20]
    Ma C, Gu C, Lian P, et al. Sulforaphane alleviates psoriasis by enhancing antioxidant defense through KEAP1-NRF2 Pathway activation and attenuating inflammatory signaling. Cell Death Dis, 2023; 14(11): 768. doi: 10.1038/s41419-023-06234-9
    [21]
    Guo D, Wang Q, Li A, et al. Liquiritin targeting Th17 cells differentiation and abnormal proliferation of keratinocytes alleviates psoriasis via NF-κB and AP-1 pathway. Phytother Res, 2024; 38(1): 174-186. doi: 10.1002/ptr.8038
    [22]
    Arican O, Aral M, Sasmaz S, et al. Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm, 2005; 2005(5): 273-279. doi: 10.1155/MI.2005.273
    [23]
    Xu H, Liu J, Niu M, et al. Soluble IL-6R-mediated IL-6 trans-signaling activation contributes to the pathological development of psoriasis. J Mol Med (Berl), 2021; 99(7): 1009-1020. doi: 10.1007/s00109-021-02073-3
    [24]
    Wu P, Ma G, Zhu X, et al. Cyr61/CCN1 is involved in the pathogenesis of psoriasis vulgaris via promoting IL-8 production by keratinocytes in a JNK/NF-κB pathway. Clin Immunol, 2017; 174: 53-62. doi: 10.1016/j.clim.2016.11.003
    [25]
    Goodman W A, Levine A D, Massari J V, et al. IL-6 signaling in psoriasis prevents immune suppression by regulatory T cells. J Immunol, 2009; 183(5): 3170-3176. doi: 10.4049/jimmunol.0803721
    [26]
    Lauffer F, Eyerich K, Boehncke W H, et al. Cytokines of the IL-17 family in psoriasis. J Dtsch Dermatol Ges, 2020; 18(7): 675-681.
    [27]
    Qazi B S, Tang K, Qazi A. Recent advances in underlying pathologies provide insight into interleukin-8 expression-mediated inflammation and angiogenesis. Int J Inflam, 2011; 2011: 908468.
    [28]
    van der Fits L, Mourits S, Voerman J S, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol, 2009; 182(9): 5836-5845. doi: 10.4049/jimmunol.0802999
    [29]
    Gangwar R S, Gudjonsson J E, Ward N L. Mouse models of psoriasis: A comprehensive review. J Invest Dermatol, 2022; 142(3 Pt B): 884-897.
    [30]
    Muntyanu A, Milan R, Kaouache M, et al. Tree-based machine learning to identify predictors of psoriasis incidence at the neighborhood level: A populational study from Quebec, Canada. Am J Clin Dermatol, 2024; 25(3): 497-508. doi: 10.1007/s40257-024-00854-3
    [31]
    Isler M F, Coates S J, Boos M D. Climate change, the cutaneous microbiome and skin disease: Implications for a warming world. Int J Dermatol, 2023; 62(3): 337-345. doi: 10.1111/ijd.16297
    [32]
    Ma F, Plazyo O, Billi A C, et al. Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis. Nat Commun, 2023; 14(1): 3455. doi: 10.1038/s41467-023-39020-4
    [33]
    Kim J, Lee J, Kim H J, et al. Single-cell transcriptomics applied to emigrating cells from psoriasis elucidate pathogenic versus regulatory immune cell subsets. J Allergy Clin Immunol, 2021; 148(5): 1281-1292. doi: 10.1016/j.jaci.2021.04.021
    [34]
    Xu Z, Chen D, Hu Y, et al. Anatomically distinct fibroblast subsets determine skin autoimmune patterns. Nature, 2022; 601(7891): 118-124. doi: 10.1038/s41586-021-04221-8
    [35]
    Chen Z, Guan D, Zhu Q, et al. Biological roles and pathogenic mechanisms of LncRNA MIR4435-2HG in cancer: A comprehensive review. Curr Issues Mol Biol, 2023; 45(11): 8864-8881. doi: 10.3390/cimb45110556
    [36]
    Wang X, Ren L, Chen S, e al. Long non-coding RNA MIR4435-2HG/microRNA-125a-5p axis is involved in myocardial ischemic injuries. Bioengineered, 2022; 13(4): 10707-10720. doi: 10.1080/21655979.2022.2051259
    [37]
    Xiao Y, Bao Y, Tang L, et al. LncRNA MIR4435-2HG is downregulated in osteoarthritis and regulates chondrocyte cell proliferation and apoptosis. J Orthop Surg Res, 2019; 14(1): 247. doi: 10.1186/s13018-019-1278-7
    [38]
    Zhang S, Li C, Liu J, et al. Fusobacterium nucleatum promotes epithelial-mesenchymal transiton through regulation of the lncRNA MIR4435-2HG/miR-296-5p/Akt2/SNAI1 signaling pathway. FEBS J, 2020; 287(18): 4032-4047. doi: 10.1111/febs.15233
    [39]
    Shen H, Sun B, Yang Y, et al. MIR4435-2HG regulates cancer cell behaviors in oral squamous cell carcinoma cell growth by upregulating TGF-β1. Odontology, 2020; 108(4): 553-559. doi: 10.1007/s10266-020-00488-x
    [40]
    Xing P, Wang Y, Zhang L, et al. Knockdown of lncRNA MIR4435‑2HG and ST8SIA1 expression inhibits the proliferation, invasion and migration of prostate cancer cells in vitro and in vivo by blocking the activation of the FAK/AKT/β‑catenin signaling pathway. Int J Mol Med, 2021; 47(6): 93. doi: 10.3892/ijmm.2021.4926
    [41]
    Yang J, Su Y, Wang Y, et al. The long noncoding RNA MIR4435-2HG enhances the migration, promotion, and glycolysis of nonsmall cell lung cancer cells by targeting the miR-371a-5p/SOX2/PI3K/Akt axis. SAGE Open Med, 2024; 12: 20503121241289290. doi: 10.1177/20503121241289290
    [42]
    Sabat R, Wolk K, Loyal L, et al. T cell pathology in skin inflammation. Semin Immunopathol, 2019; 41(3): 359-377. doi: 10.1007/s00281-019-00742-7
    [43]
    Liu L, Zhou Y, Luo D, et al. Aberrant promoter methylation of Wnt inhibitory factor-1 gene is a potential target for treating psoriasis. Clin Immunol, 2023; 250: 109294. doi: 10.1016/j.clim.2023.109294
    [44]
    Niedźwiedź M, Skibińska M, Ciążyńska M, et al. Psoriasis and seasonality: Exploring the genetic and epigenetic interactions. Int J Mol Sci, 2024; 25(21): 11670. doi: 10.3390/ijms252111670
    [45]
    Dopico X C, Evangelou M, Ferreira R C, et al. Widespread seasonal gene expression reveals annual differences in human immunity and physiology. Nat Commun, 2015; 6: 7000. doi: 10.1038/ncomms8000
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