Expression of β-catenin in Skin Lesions of Patients with Scleroderma and Its Effect on Epithelial-Mesenchymal Transition of Human Epidermal Keratinocytes

LIU Jin-juan, YANG Hong-fa, LI Yong-jian, CHEN Yan-ming

Abstract

To investigate the expression of β-catenin in the skin lesions of patients with systemic scleroderma (SSc) and its effect on epithelial-mesenchymal transition (EMT) of human epidermal keratinocytes.  Methods  The expression of β-catenin, Snail1 and E-cadherin in the skin lesions sample of 45 SSc patients and normal skin sample from 20 healthy adults was detected with SP immunohistochemistry. HaCaT, the human epidermal keratinocytes, were treated with different concentrations of Wnt10b (0 ng/mL (control), 2 ng/mL and 4 ng/mL) for 48 h. then detected the localization of β-catenin in HaCaT cells by immunofluorescence assay, determined the mRNA levels of Snail1 and Snail2 in HaCaT cells by real-time fluorescent quantitative PCR, detected the proteins expression of β-catenin, Vimentin, N-cadherin and E-cadherin in HaCaT cells by Western blot.  Results  The positive rates of β-catenin, Snail1 and E-cadherin in skin lesions of SSc patients were 100%, 88.89% and 2.22% respectively, while in healthy adult skin, the corresponding positive rates were 0%, 10.00%, and 95.00%. The difference between the two groups was significant. Compared with control group, treatment with different concentrations of Wnt10b (2 ng/mL and 4 ng/mL) induced up-regulation of β-catenin expression and promoted translocation of β-catenin from cytoplasm to nucleus, increased the mRNA levels of Snail1 and Snail2 (P < 0.05), and up-regulated the proteins expression of Vimentin, N-cadherin, down-regulated the E-cadherin protein expression in HaCaT cells (P < 0.05).  Conclusion  Abnormally activated Wnt/β-catenin signaling pathway and abnormally expressed EMT-related proteins are observed in SSc lesions. Activation of Wnt/β-catenin signaling pathway may promote EMT in HaCaT cells.

 

Keywords: β-catenin, Systemic scleroderma, Wnt/β-catenin signaling pathway, Epithelial-mesenchymal transition

 

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References


ORLANDI M. BARSOTTI S, LEPRI G, et al. One year in review 2018; systemic sclerosis. Clin Exp Rheumatol,2018, 36 Suppl 113(4);3-23.

RUBIORIVAS M.ROYO C,SIMEON С P.et al. Mortality and survival in systemic sclerosis; systematic review and meta-analysis. Semin Arthritis Rheum, 2014, 44 ( 2 ): 208- 219.

WERNIG GXHEN S Y.CUI L.et al. Unifying mechanism for different fibrotic diseases. Proc Natl Acad Sci U S A, 2017,114(18);4757-4762.

2018,38(09) :1329-1332. MANETTI М,ROMANO E,ROSA U, et al. Endothelial-to- mesenchymal transition contributes to endothelial dysfunction and dermal fibrosis in systemic sclerosis. Ann Rheum Dis, 2017,76(5):924-934.

PIERA-VELAZQUEZ S. MENDOZA F A, JIMENEZ S A. Endothelial to mesenchymal transition ( EndoMT) in the pathogenesis of human fibrotic diseases. J Clin Med, 2016, 5 (4):45-67.

SONG Y, LI Z X, LIU X, et al. The Wnt/jJ-catenin and PI3K/Akt signaling pathways promote EMT in gastric cancer by epigenetic regulation via H3 lysine 27 acetylation. Tumour Biol.2017.39(7): 1010428317712617[2018-12-05]. https:// doi. org/10. 1177/1010428317712617.

YU , LI Q. SHI G, et al. Involvement of epithelial- mesenchymal transition in liver fibrosis. Saudi J Gastroenterol,2018,24( 1);5-11.

GEYER M. MULLER-LADNER U. The pathogenesis of systemic sclerosis revisited. Clin Rev Allergy Immunol,2011, 40(2):92-103.

NOGRADI A.PORPACZY A.PORCSA U, et al. Relation of right atrial mechanics to functional capacity in patients with systemic sclerosis. Am J Cardiol,2018,122(7): 1249-1254.

KOGUCHI N, OKADA A, CHOH S, et al. Concomitant systemic sclerosis and sarcoidosis with combined pulmonary fibrosis and emphysema. Intern Med, 2016, 55 ( 10 ); 1331- 1335.

SHAH J, SHAHIDULLAH A. Chronic intestinal pseudo-obstruction in systemic sclerosis: an uncommon presentation. Case Rep Gastroenterol,2018,12(2);373-378.

AKCORA BO, STORM G, BANSAL R, Inhibition of canonical WNT signaling pathway by beta-catenin/CBP inhibitor ICG-001 ameliorates liver fibrosis in vivo through suppression of stromal CXCL12. Biochim Biophys Acta Mol Basis Dis,2018,1864(3):804-818.

КАТО N. SHIMMURA S. К AW AKITA T, et al. Beta- catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium. Invest Ophthalmol Vis Sci,2007, 48(4);1511-1517.

WEI J.MELICHIAN D.KOMURA K.eial. Canonical Wnt signaling induces skin fibrosis and subcutaneous lipoatrophy: a novel mouse model for scleroderma, Arthritis Rheum, 2011,63(6);1707-1717.

FROST J.ESTIVILL X. RAMSAY M ,et al. Dysregulation of the Wnt signaling pathway in South African patients with diffuse systemic sclerosis. Clin Rheumatol, 2019 , 38( 3): 933- 938.

CRUZ-SOLBES A S, YOUKER К. Epithelial to mesenchymal transition ( EMT ) and endothelial to mesenchymal transition (EndMT): role and implications in kidney fibrosis. Results Probl Cell Differ, 2017, 60; 345-372 Г 2018-12-05 ]. https://link. springer, com/chapter/10. 1007% 2F978-3-319-51436-9 _ 13. doi: 10. 1007/978-3-319- 51436-9_13.


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