Articles
Vol. 70 No. 3 (2026)
https://doi.org/10.4081/ejh.2026.4606

SPRR2B knockdown inhibits the proliferation and inflammatory response in M5-treated human HaCaT keratinocytes

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Published: 6 August 2026
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psoriasis, SPRR2B, HaCaT, JAK1, MDM2, p53

Authors

Zhenzhen Ding
Department of Dermatology, The Affiliated Yangming Hospital of Ningbo University (Yuyao People's Hospital), Yuyao, China.
Chengchi Wang
Department of Dermatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Mingfeng Lv
lvmingfen1106@163.com
Department of Dermatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and excessive immune activation, for which curative therapies remain limited. This study aimed to investigate the role of small proline-rich protein 2B (SPRR2B) in psoriasis pathogenesis. In this study, gene Expression Omnibus (GEO) dataset GSE13355 was analyzed using R Language. Cell proliferation, gene and protein expression were measured with CCK8, RT-qPCR and immunofluorescence staining, respectively. Bioinformatics analysis of the GSE13355 dataset revealed that SPRR2B was significantly overexpressed in psoriatic lesions and was positively correlated with immune cell infiltration and multiple inflammatory pathways. In an M5-induced HaCaT keratinocyte psoriatic model, SPRR2B knockdown markedly suppressed cell proliferation and promoted apoptosis via regulation of the MDM2/p53/CDKN1A axis. Furthermore, SPRR2B knockdown reduced the secretion of IL-6, IFN-γ, TNF-α, and IL-1β, and inhibited JAK1 phosphorylation. These findings demonstrated that SPRR2B promotes keratinocyte proliferation and inflammatory response in psoriasis, suggesting it may serve as a promising diagnostic biomarker and therapeutic target for the disease.

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Europe PMC
1.Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med 2009;361:496-509. DOI: https://doi.org/10.1056/NEJMra0804595
2.Boehncke WH, Schön MP. Psoriasis. Lancet 2015;386:983-94. DOI: https://doi.org/10.1016/S0140-6736(14)61909-7
3.Furue K, Ito T, Tsuji G, Kadono T, Furue M. Psoriasis and the TNF/IL23/IL17 axis. G Ital Dermatol Venereol 2019;154:418-24. DOI: https://doi.org/10.23736/S0392-0488.18.06202-8
4.Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis: a review. JAMA 2020;323:1945-60. DOI: https://doi.org/10.1001/jama.2020.4006
5.Gibbs S, Fijneman R, Wiegant J, van Kessel AG, van De Putte P, Backendorf C. Molecular characterization and evolution of the SPRR family of keratinocyte differentiation markers encoding small proline-rich proteins. Genomics 1993;16:630-7. DOI: https://doi.org/10.1006/geno.1993.1240
6.Burke RM, Lighthouse JK, Quijada P, Dirkx RA Jr, Rosenberg A, Moravec CS, et al. Small proline-rich protein 2B drives stress-dependent p53 degradation and fibroblast proliferation in heart failure. Proc Natl Acad Sci U S A 2018;115:E3436-E45. DOI: https://doi.org/10.1073/pnas.1717423115
7.Kim J, Deshar B, Hwang M, Shrestha C, Ju E, Bin BH, et al. Quantum molecular resonance ameliorates atopic dermatitis through suppression of IL36G and SPRR2B. BMB Rep 2025;58:209-16. DOI: https://doi.org/10.5483/BMBRep.2024-0105
8.Xue C, Yao Q, Gu X, Shi Q, Yuan X, Chu Q, et al. Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer. Signal Transduct Target Ther 2023;8:204. DOI: https://doi.org/10.1038/s41392-023-01468-7
9.Sugumaran D, Yong ACH, Stanslas J. Advances in psoriasis research: from pathogenesis to therapeutics. Life Sci 2024;355:122991. DOI: https://doi.org/10.1016/j.lfs.2024.122991
10.Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods 2015;12:453-7. DOI: https://doi.org/10.1038/nmeth.3337
11.Dull K, Lénárt K, Dajnoki Z, Póliska S, Uchiyama E, Hendrik Z, et al. Barrier function-related genes and proteins have an altered expression in acne-involved skin. J Eur Acad Dermatol Venereol 2023;37:1415-25. DOI: https://doi.org/10.1111/jdv.19062
12.Barygina V, Becatti M, Prignano F, Lotti T, Taddei N, Fiorillo C. Fibroblasts to keratinocytes redox signaling: the possible role of ROS in psoriatic plaque formation. Antioxidants (Basel) 2019;8:11. DOI: https://doi.org/10.3390/antiox8110566
13.Yao L, Yan J, Cheng F, Gan L, Huang Y, Zheng L, et al. Small proline-rich protein 2B facilitates gastric adenocarcinoma proliferation via MDM2-p53/p21 signaling pathway. Onco Targets Ther 2021;14:1453-63. DOI: https://doi.org/10.2147/OTT.S281032
14.Dębińska A, Danielewicz H, Boznański A, Matusiak Ł, Szepietowski JC. A small proline-rich protein (SPRR) gene variant contributes to atopic eczema and eczema-associated asthma susceptibility. Postepy Dermatol Alergol 2022;39:965-71. DOI: https://doi.org/10.5114/ada.2022.113145
15.Gong X, Wang W. Profiles of innate immune cell infiltration and related core genes in psoriasis. BioMed Res Int 2021;2021:6656622. DOI: https://doi.org/10.1155/2021/6656622
16.Giraulo C, De Palma G, Plaitano P, Esposito R, Morretta E, Monti MC, et al. Oncostatin M upregulates CD73 via the MAPK pathway in keratinocytes to promote an adenosine-dependent anti-inflammatory response in psoriasis. Front Immunol 2026;17:1698290. DOI: https://doi.org/10.3389/fimmu.2026.1698290
17.Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004;303:844-8. DOI: https://doi.org/10.1126/science.1092472
18.Ma R, Cui L, Cai J, Yang N, Wang Y, Chen Q, et al. Association between systemic immune inflammation index, systemic inflammation response index and adult psoriasis: evidence from NHANES. Front Immunol 2024;15:1323174. DOI: https://doi.org/10.3389/fimmu.2024.1323174
19.Svedbom A, Mallbris L, González-Cantero Á, Playford M, Wu C, Mehta NN, et al. Skin inflammation, systemic inflammation, and cardiovascular disease in psoriasis. JAMA Dermatol 2025;161:81-6. DOI: https://doi.org/10.1001/jamadermatol.2024.4433

CRediT authorship contribution

Zhenzhen Ding, conceptualization, methodology, investigation, supervision, writing – original draft. Mingfen Lv, conceptualization, methodology, supervision, validation, data curation, writing – original draft. Chengchi Wang, investigation, data curation, formal analysis. All authors have read and approved the final version of the manuscript.

Supporting Agencies

The First Affiliated Hospital of Wenzhou Medical University

Data Availability Statement

The data used to support the findings of this study are available from the corresponding author on reasonable request.

How to Cite



1.
Ding Z, Wang C, Lv M. SPRR2B knockdown inhibits the proliferation and inflammatory response in M5-treated human HaCaT keratinocytes. Eur J Histochem [Internet]. 2026 Aug. 6 [cited 2026 Aug. 14];70(3). Available from: https://www.ejh.it/ejh/article/view/4606
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