Role of overexpression of microRNA-31 and its downstream target genes Sfn and SuFu in animal models of psoriasis

Jing Zhijie, Fu Mingyang, Wang Chunfang

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Journal of Chongqing Medical University ›› 2024, Vol. 49 ›› Issue (11) : 1394-1401. DOI: 10.13406/j.cnki.cyxb.003630
Basic research

Role of overexpression of microRNA-31 and its downstream target genes Sfn and SuFu in animal models of psoriasis

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Abstract

Objective To investigate the role of intrinsic overexpression of microRNA-31(miR-31) and its downstream target genes Stratifin (Sfn) and Suppressor of Fused(SuFu) in the development and progression of psoriasis induced by imiquimod(IMQ) in a mouse model. Methods The literature and PubMed were searched to identify the genes associated with psoriasis,and Target Scan Human database was used to predict the target genes of miR-31. IMQ cream was used to induce psoriasis in wild-type FVB mice and miR-31 transgenic mice; images of the dorsal skin were collected from these model mice daily,and the PASI score was used to evaluate the severity of psoriasis. HE staining was used to observe histomorphological changes. The dorsal skin of the mice was collected on days 0,3,and 7,and RT-PCR was used to measure the mRNA expression levels of miR-31 and its downstream target genes. Two target genes were identified and analyzed by immunofluorescence assay and Western blot. Results The Target Scan Human database predicted eight downstream target genes of miR-31,and quantitative real-time PCR obtained two target genes associated with psoriasis,i.e.,Sfn and SuFu. IMQ induced psoriasis-like symptoms in mice,including erythema,scales,and epidermal thickening of the dorsal skin. The experimental results showed that the miR-31 experimental group had milder psoriatic symptoms than the wild-type FVB experimental group,which was confirmed by HE staining. RT-PCR was used to measure the expression levels of miR-31,Sfn,and SuFu on days 3 and 7,and the results showed an increase in the expression of miR-31 in wild-type FVB mice and a reduction in miR-31 transgenic mice,while the expression levels of its target genes Sfn and SuFu showed opposite changes. The results of immunofluorescence assay and Western blot results were consistent with the results of PCR. Conclusion In the animal model of psoriasis,there are weak psoriatic symptoms in the skin with intrinsic overexpression of miR-31,and it may reduce the severity of psoriasis in combination with the organs associated with psoriasis in the body through the intrinsic overexpression of miR-31. Sfn and SuFu are the downstream target genes of miR-31 and may play an inhibitory role in the pathogenesis of psoriasis.

Key words

microRNA-31 / psoriasis / suppressor of Fused / Stratifin

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Jing Zhijie , Fu Mingyang , Wang Chunfang. Role of overexpression of microRNA-31 and its downstream target genes Sfn and SuFu in animal models of psoriasis. Journal of Chongqing Medical University. 2024, 49(11): 1394-1401 https://doi.org/10.13406/j.cnki.cyxb.003630

References

1
Schön MP Boehncke WH. Psoriasis[J]. N Engl J Med2005352(18):1899-1912.
2
Lowes MA Bowcock AM Krueger JG. Pathogenesis and therapy of psoriasis[J]. Nature2007445(7130):866-873.
3
Xia J Joyce CE Bowcock AM,et al. Noncanonical microRNAs and endogenous siRNAs in normal and psoriatic human skin[J]. Hum Mol Genet201322(4):737-748.
4
Fabian MR Sonenberg N Filipowicz W. Regulation of mRNA translation and stability by microRNAs[J]. Annu Rev Biochem201079:351-379.
5
唐雪勇. 银屑病皮损组织中miRNA的差异表达分析及竹黄颗粒剂对其的干预作用[D]. 长沙:湖南中医药大学,2012
Tang XY. Study on the Differential Exppession of MiRNA in Psoriatic Skin and the Intervention Effects of ZhuHuang Granule[D]. Changsha:Hunan University of Chinese Medicine,2012
6
Endo H Momota Y Oikawa A,et al. Psoriatic skin expresses the transcription factor Gli1:possible contribution of decreased neurofibromin expression[J]. Br J Dermatol2006154(4):619-623.
7
Fan H Khavari PA. Sonic hedgehog opposes epithelial cell cycle arrest[J]. J Cell Biol1999147(1):71-76.
8
Hermeking H Benzinger A. 14-3-3 proteins in cell cycle regulation[J]. Semin Cancer Biol200616(3):183-192.
9
Conklin DS Galaktionov K Beach D. 14-3-3 proteins associate with cdc25 phosphatases[J]. Proc Natl Acad Sci USA,1995,92(17):7892-7896.
10
Laronga C Yang HY Neal C,et al. Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression[J]. J Biol Chem2000275(30):23106-23112.
11
Sabat R Sterry W Philipp S,et al. Three decades of psoriasis research:where has it led us?[J]. Clin Dermatol200725(6):504-509.
12
Xu N Meisgen F Butler LM,et al. MicroRNA-31 is overexpressed in psoriasis and modulates inflammatory cytokine and chemokine production in keratinocytes via targeting serine/threonine kinase 40[J]. J Immunol2013190(2):678-688.
13
Balato N Napolitano M Ayala F,et al. Nonalcoholic fatty liver disease,spleen and psoriasis:new aspects of low-grade chronic inflammation[J]. World J Gastroenterol201521(22):6892-6897.
14
Dowlatshahi EA van der Voort EA Arends LR,et al. Markers of systemic inflammation in psoriasis:a systematic review and meta-analysis[J]. Br J Dermatol2013169(2):266-282.
15
Balato A di Caprio R Canta L,et al. IL-33 is regulated by TNF-α in normal and psoriatic skin[J]. Arch Dermatol Res2014306(3):299-304.
16
Ghazizadeh R Shimizu H Tosa M,et al. Pathogenic mechanisms shared between psoriasis and cardiovascular disease[J]. Int J Med Sci20107(5):284-289.
17
Davidovici BB Sattar N Prinz J,et al. Psoriasis and systemic inflammatory diseases:potential mechanistic links between skin disease and co-morbid conditions[J]. J Invest Dermatol2010130(7):1785-1796.
18
Dai RJ Zhang Y Khan D,et al. Identification of a common lupus disease-associated microRNA expression pattern in three different murine models of lupus[J]. PLoS One20105(12):e14302.
19
Li ZM Liu JY Zhang JT. 14-3-3sigma,the double-edged sword of human cancers[J]. Am J Transl Res20091(4):326-340.
20
Wrone-Smith T Johnson T Nelson B,et al. Discordant expression of Bcl-x and Bcl-2 by keratinocytes in vitro and psoriatic keratinocytes in vivo [J]. Am J Pathol1995146(5):1079-1088.
21
Bianchi L Farrace MG Nini G,et al. Abnormal Bcl-2 and “tissue” transglutaminase expression in psoriatic skin[J]. J Invest Dermatol1994103(6):829-833.
22
Soini Y Kamel D Pääkkö P,et al. Aberrant accumulation of p53 associates with Ki67 and mitotic count in benign skin lesions[J]. Br J Dermatol1994131(4):514-520.
23
Moorchung N Vasudevan B Dinesh Kumar S,et al. Expression of apoptosis regulating proteins p53 and bcl-2 in psoriasis[J]. Indian J Pathol Microbiol201558(4):423-426.
24
Dahmane N Lee J Robins P,et al. Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours[J]. Nature1997389(6653):876-881.
25
曹华莉. Hedgehog信号通路在银屑病发病中的机制研究[D]. 杭州:浙江大学,2015
Cao HL. Role of Hedgehog Signaling Pathway in Psoriasis[D]. Hangzhou:Zhejiang University,2015
26
Liu HY Jian Q Xue K,et al. The MEK/ERK signalling cascade is required for sonic hedgehog signalling pathway-mediated enhancement of proliferation and inhibition of apoptosis in normal keratinocytes[J]. Exp Dermatol201423(12):896-901.

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