Interaction of Wnt5a with Notch1 is Critical for the Pathogenesis of Psoriasis

Overview

Journal Ann Dermatol

Specialty Dermatology

Date 2016 Feb 6

PMID 26848218

Citations 8

Authors

Jeong Eun Kim

Seung Hyun Bang

Jee Ho Choi

Chang Deok Kim

Chong Hyun Won

Mi Woo Lee

Sung Eun Chang

Affiliations

Soon will be listed here.

Abstract

Background: Psoriasis is characterized by uncontrolled hyperproliferation, aberrant differentiation, and dermal infiltration of immune cells. Recent studies have reported that Wnt5a and Notch1 signaling are altered in psoriatic skin lesions.

Objective: We aimed to investigate the interaction of Wnt5a with Notch 1 with respect to inflammation-mediated epidermal hyperproliferation in psoriasis.

Methods: Expression of Wnt5a and Notch1 signaling-related proteins were examined in psoriatic skin biopsies. Wnt5a was upregulated in human keratinocytes by treating the cells with its recombinant form (rWnt5a).

Results: In psoriatic lesions, expression of Wnt5a increased while that of Notch1 decreased when compared to that in non-lesional and normal skin. Treatment with rWnt5a increased the proliferation of keratinocytes and increased their secretion of interleukin (IL)-23, IL-12, and tumor necrosis factor (TNF)-α. Further, exposure of keratinocytes to IL-1α, TNF-α, transforming growth factor-α, and interferon-γ downregulated Notch1 as well as HES 1, which is downstream to Notch1, but increased the Wnt5a levels. The upregulated Wnt5a in keratinocytes downregulated both Notch1 and HES1.

Conclusion: Our data suggest that Wnt5a and Notch1 signaling exert counteracting influences on each other and are involved, in part, in the pathomechanism of psoriasis.

Citing Articles

Momordin Ic ameliorates psoriasis skin damage in mice via the IL-23/IL-17 axis.

Wang C, Jiao S, Zhou R, Huang P, Zeng B, Yang Z Arch Dermatol Res. 2024; 316(7):474.

PMID: 39007937 DOI: 10.1007/s00403-024-03023-y.

AIM2 and Psoriasis.

Zhang Y, Xu X, Cheng H, Zhou F Front Immunol. 2023; 14:1085448.

PMID: 36742336 PMC: 9889639. DOI: 10.3389/fimmu.2023.1085448.

Targeting the transcription factor HES1 by L-menthol restores protein phosphatase 6 in keratinocytes in models of psoriasis.

Wang Z, Sun Y, Lou F, Bai J, Zhou H, Cai X Nat Commun. 2022; 13(1):7815.

PMID: 36535970 PMC: 9763329. DOI: 10.1038/s41467-022-35565-y.

Investigation on the Inhibitory Effect of Wnt-5a on Colonic Mucosal Inflammation in Patients with Ulcerative Colitis.

Uchiyama K, Takagi T, Mizushima K, Asaeda K, Kajiwara M, Kashiwagi S Dig Dis Sci. 2022; 67(10):4760-4769.

PMID: 35590045 DOI: 10.1007/s10620-022-07537-1.

The value of as prognostic and immunological biomarker in pan-cancer.

Feng Y, Wang Y, Guo K, Feng J, Shao C, Pan M Ann Transl Med. 2022; 10(8):466.

PMID: 35571400 PMC: 9096401. DOI: 10.21037/atm-22-1317.

References

Reischl J, Schwenke S, Beekman J, Mrowietz U, Sturzebecher S, Heubach J . Increased expression of Wnt5a in psoriatic plaques. J Invest Dermatol. 2006; 127(1):163-9. DOI: 10.1038/sj.jid.5700488. View

Blaumueller C, Qi H, Zagouras P, Artavanis-Tsakonas S . Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane. Cell. 1997; 90(2):281-91. DOI: 10.1016/s0092-8674(00)80336-0. View

Lefort K, Mandinova A, Ostano P, Kolev V, Calpini V, Kolfschoten I . Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKalpha kinases. Genes Dev. 2007; 21(5):562-77. PMC: 1820898. DOI: 10.1101/gad.1484707. View

Romanowska M, Evans A, Kellock D, Bray S, McLean K, Donandt S . Wnt5a exhibits layer-specific expression in adult skin, is upregulated in psoriasis, and synergizes with type 1 interferon. PLoS One. 2009; 4(4):e5354. PMC: 2670517. DOI: 10.1371/journal.pone.0005354. View

Suarez-Farinas M, Fuentes-Duculan J, Lowes M, Krueger J . Resolved psoriasis lesions retain expression of a subset of disease-related genes. J Invest Dermatol. 2010; 131(2):391-400. PMC: 3021088. DOI: 10.1038/jid.2010.280. View

Pereira C, Schaer D, Bachli E, Kurrer M, Schoedon G . Wnt5A/CaMKII signaling contributes to the inflammatory response of macrophages and is a target for the antiinflammatory action of activated protein C and interleukin-10. Arterioscler Thromb Vasc Biol. 2008; 28(3):504-10. DOI: 10.1161/ATVBAHA.107.157438. View

Nicolas M, Wolfer A, Raj K, Kummer J, Mill P, van Noort M . Notch1 functions as a tumor suppressor in mouse skin. Nat Genet. 2003; 33(3):416-21. DOI: 10.1038/ng1099. View

Kim J, Won C, Bak H, Kositratna G, Manstein D, Dotto G . Gene profiling analysis of the early effects of ablative fractional carbon dioxide laser treatment on human skin. Dermatol Surg. 2013; 39(7):1033-43. DOI: 10.1111/dsu.12170. View

Ann E, Kim H, Seo M, Mo J, Kim M, Yoon J . Wnt5a controls Notch1 signaling through CaMKII-mediated degradation of the SMRT corepressor protein. J Biol Chem. 2012; 287(44):36814-29. PMC: 3481284. DOI: 10.1074/jbc.M112.356048. View

10.

Iizuka H, Takahashi H, Honma M, Ishida-Yamamoto A . Unique keratinization process in psoriasis: late differentiation markers are abolished because of the premature cell death. J Dermatol. 2004; 31(4):271-6. DOI: 10.1111/j.1346-8138.2004.tb00672.x. View

11.

Zhu X, Wu Y, Huang S, Chen Y, Tao Y, Wang Y . Overexpression of Wnt5a in mouse epidermis causes no psoriasis phenotype but an impairment of hair follicle anagen development. Exp Dermatol. 2014; 23(12):926-8. DOI: 10.1111/exd.12539. View

12.

Masckauchan T, Agalliu D, Vorontchikhina M, Ahn A, Parmalee N, Li C . Wnt5a signaling induces proliferation and survival of endothelial cells in vitro and expression of MMP-1 and Tie-2. Mol Biol Cell. 2006; 17(12):5163-72. PMC: 1679681. DOI: 10.1091/mbc.e06-04-0320. View

13.

Katoh M, Katoh M . Transcriptional mechanisms of WNT5A based on NF-kappaB, Hedgehog, TGFbeta, and Notch signaling cascades. Int J Mol Med. 2009; 23(6):763-9. DOI: 10.3892/ijmm_00000190. View

14.

Gudjonsson J, Johnston A, Stoll S, Riblett M, Xing X, Kochkodan J . Evidence for altered Wnt signaling in psoriatic skin. J Invest Dermatol. 2010; 130(7):1849-59. PMC: 2886156. DOI: 10.1038/jid.2010.67. View

15.

Thelu J, Rossio P, Favier B . Notch signalling is linked to epidermal cell differentiation level in basal cell carcinoma, psoriasis and wound healing. BMC Dermatol. 2002; 2:7. PMC: 111189. DOI: 10.1186/1471-5945-2-7. View

16.

Nguyen B, Lefort K, Mandinova A, Antonini D, Devgan V, Della Gatta G . Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation. Genes Dev. 2006; 20(8):1028-42. PMC: 1472299. DOI: 10.1101/gad.1406006. View

17.

Koyanagi M, Bushoven P, Iwasaki M, Urbich C, Zeiher A, Dimmeler S . Notch signaling contributes to the expression of cardiac markers in human circulating progenitor cells. Circ Res. 2007; 101(11):1139-45. DOI: 10.1161/CIRCRESAHA.107.151381. View

18.

Couso J, Arias A . Notch is required for wingless signaling in the epidermis of Drosophila. Cell. 1994; 79(2):259-72. DOI: 10.1016/0092-8674(94)90195-3. View

19.

Collins B, Kleeberger W, Ball D . Notch in lung development and lung cancer. Semin Cancer Biol. 2004; 14(5):357-64. DOI: 10.1016/j.semcancer.2004.04.015. View

20.

van Amerongen R, Mikels A, Nusse R . Alternative wnt signaling is initiated by distinct receptors. Sci Signal. 2008; 1(35):re9. DOI: 10.1126/scisignal.135re9. View