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

doi:10.13406/j.cnki.cyxb.003630

您当前的位置：

首页 >

文章列表页 >

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

Basic research | 更新时间：2025-10-23

- Role of overexpression of microRNA-31 and its downstream target genes Sfn and SuFu in animal models of psoriasis
- Journal of Chongqing Medical University Vol. 49, Issue 11, Pages: 1394-1401(2024)
- 作者机构：
  
  山西医科大学实验动物中心/实验动物与人类疾病动物模型山西省重点实验室，太原 030001
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003630
  CLC： R758.63
- Received：01 December 2023，
  
  Revised：2024-08-02，
  
  Accepted：28 August 2024，
  
  Published：28 November 2024
- 稿件说明：
移动端阅览
景志杰,付明阳,王春芳.过表达miR-31及其下游靶基因Sfn、SuFu在银屑病动物模型中的作用[J].重庆医科大学学报,2024,49(11):1394-1401.

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[J].Journal of Chongqing Medical University,2024,49(11):1394-1401.
景志杰,付明阳,王春芳.过表达miR-31及其下游靶基因Sfn、SuFu在银屑病动物模型中的作用[J].重庆医科大学学报,2024,49(11):1394-1401. DOI： 10.13406/j.cnki.cyxb.003630.

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[J].Journal of Chongqing Medical University,2024,49(11):1394-1401. DOI： 10.13406/j.cnki.cyxb.003630.

摘要

目的

研究内在过表达miR-31及其下游靶基因Sfn、SuFu在咪喹莫特诱导的小鼠银屑病模型发生发展中的作用。

方法

从文献及PubMed收集与银屑病相关基因，使用Target Scan Human数据库预测miR-31靶基因。使用咪喹莫特乳膏对野生型FVB小鼠和miR-31转基因小鼠进行银屑病造模，每日采集造模小鼠背部变化图像，随后使用PASI评分评价小鼠银屑病样情况。HE染色观察组织形态学变化。取0 d、3 d、7 d模型小鼠的背部皮肤，随后进行RT-PCR检测miR-31及其下游靶基因mRNAs的表达，筛选出2个miR-31靶基因，并对筛选靶基因进行免疫荧光及Western blot检测分析。

结果

Target Scan Human数据库预测出8个miR-31下游靶基因，经荧光定量PCR筛选出2个与银屑病相关靶基因Sfn、SuFu。咪喹莫特诱导小鼠产生银屑病样症状，表现为背部出现红斑、银白鳞屑，表皮增厚等，实验结果显示miR-31实验组较野生型FVB实验组银屑病样症状轻，HE染色切片同样证实此情况。RT-PCR检测3 d、7 d时miR-31，Sfn和SuFu的表达，结果显示野生型FVB小鼠miR-31的表达均升高，而miR-31转基因小鼠miR-31的表达却降低，其靶基因Sfn、SuFu均出现相反情况，免疫荧光及western blot结果均与PCR结果一致。

结论

在银屑病动物模型中，内在过表达miR-31的皮肤，其银屑病样症状较弱，它可能联合机体内与银屑病相关的器官通过内在过表达miR-31的调控作用而减弱银屑病严重程度。Sfn、SuFu作为miR-31下游靶基因，可能在银屑病的发病过程中起抑制作用。

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.

关键词

Keywords

references

Schön MP ， Boehncke WH . Psoriasis [J ] . N Engl J Med ， 2005 ， 352 （ 18 ）： 1899 - 1912 ．

Lowes MA ， Bowcock AM ， Krueger JG . Pathogenesis and therapy of psoriasis [J ] . Nature ， 2007 ， 445 （ 7130 ）： 866 - 873 ．

Xia J ， Joyce CE ， Bowcock AM ， et al . Noncanonical microRNAs and endogenous siRNAs in normal and psoriatic human skin [J ] . Hum Mol Genet ， 2013 ， 22 （ 4 ）： 737 - 748 ．

Fabian MR ， Sonenberg N ， Filipowicz W . Regulation of mRNA translation and stability by microRNAs [J ] . Annu Rev Biochem ， 2010 ， 79 ： 351 - 379 ．

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 ．

Endo H ， Momota Y ， Oikawa A ， et al . Psoriatic skin expresses the transcription factor Gli1：possible contribution of decreased neurofibromin expression [J ] . Br J Dermatol ， 2006 ， 154 （ 4 ）： 619 - 623 ．

Fan H ， Khavari PA . Sonic hedgehog opposes epithelial cell cycle arrest [J ] . J Cell Biol ， 1999 ， 147 （ 1 ）： 71 - 76 ．

Hermeking H ， Benzinger A . 14-3-3 proteins in cell cycle regulation [J ] . Semin Cancer Biol ， 2006 ， 16 （ 3 ）： 183 - 192 ．

Conklin DS ， Galaktionov K ， Beach D . 14 - 3 - 3 proteins associate with cdc 25 phosphatases [J ] . Proc Natl Acad Sci USA ，1995， 92 （ 17 ）： 7892 - 7896 ．

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 Chem ， 2000 ， 275 （ 30 ）： 23106 - 23112 ．

Sabat R ， Sterry W ， Philipp S ， et al . Three decades of psoriasis research：where has it led us? [J ] . Clin Dermatol ， 2007 ， 25 （ 6 ）： 504 - 509 ．

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 Immunol ， 2013 ， 190 （ 2 ）： 678 - 688 ．

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 Gastroenterol ， 2015 ， 21 （ 22 ）： 6892 - 6897 ．

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 Dermatol ， 2013 ， 169 （ 2 ）： 266 - 282 ．

Balato A ， di Caprio R ， Canta L ， et al . IL-33 is regulated by TNF-α in normal and psoriatic skin [J ] . Arch Dermatol Res ， 2014 ， 306 （ 3 ）： 299 - 304 ．

Ghazizadeh R ， Shimizu H ， Tosa M ， et al . Pathogenic mechanisms shared between psoriasis and cardiovascular disease [J ] . Int J Med Sci ， 2010 ， 7 （ 5 ）： 284 - 289 ．

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 Dermatol ， 2010 ， 130 （ 7 ）： 1785 - 1796 ．

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 One ， 2010 ， 5 （ 12 ）： e14302 ．

Li ZM ， Liu JY ， Zhang JT . 14-3-3sigma，the double-edged sword of human cancers [J ] . Am J Transl Res ， 2009 ， 1 （ 4 ）： 326 - 340 ．

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 Pathol ， 1995 ， 146 （ 5 ）： 1079 - 1088 ．

Bianchi L ， Farrace MG ， Nini G ， et al . Abnormal Bcl-2 and “tissue” transglutaminase expression in psoriatic skin [J ] . J Invest Dermatol ， 1994 ， 103 （ 6 ）： 829 - 833 ．

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 Dermatol ， 1994 ， 131 （ 4 ）： 514 - 520 ．

Moorchung N ， Vasudevan B ， Dinesh Kumar S ， et al . Expression of apoptosis regulating proteins p53 and bcl-2 in psoriasis [J ] . Indian J Pathol Microbiol ， 2015 ， 58 （ 4 ）： 423 - 426 ．

Dahmane N ， Lee J ， Robins P ， et al . Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours [J ] . Nature ， 1997 ， 389 （ 6653 ）： 876 - 881 ．

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 ．

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 Dermatol ， 2014 ， 23 （ 12 ）： 896 - 901 ．

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

No data

Related Author

Huang Yixia

Zhang Huiyun

Wang Wei

Yang Ruiming

He Shaoheng

Ke Meiling

Yu Weihua

Cai Tao

Related Institution

Allergy and Clinical Immunology Research Centre,The First Affiliated Hospital of Jinzhou Medical University

Centre of Neuroscience,Chongqing Medical University

Department of Dermatology,The First Affiliated Hospital of Chongqing Medical University

Department of Geriatrics,The First Affiliated Hospital of Chongqing Medical University

⁰