TINCR-MAF：MAFB转录因子网络对人角质形成细胞增殖和分化的影响

doi:10.3969/j.issn.1006-5725.2025.04.007

Abstract

Abstract:

Objective To explore the impact of the TINCR-MAF：MAFB transcription factor network on the expression of proliferation and differentiation-related genes in keratinocytes， to verify the role of this network in the occurrence and development of psoriasis and its potential mechanisms. Methods Employed RNA interference technology to knock down TINCR gene expression， and the proliferation ability of keratinocytes was assessed using the CCK-8 method. Additionally， qRT-PCR and Western blot analyses were conducted to evaluate the RNA and protein expression levels of TINCR， MAFB， and KLF4 genes. Immunohistochemical methods were used to detect the expression of KLF4 protein in psoriasis tissues. Results After TINCR gene siRNA interference， the proliferation ability of keratinocytes significantly decreased at 24， 48， and 72 hours （P < 0.001）， indicating that the TINCR gene plays a critical role in cell proliferation. The results of qRT-PCR and Western blot analyses showed that the RNA and protein expression levels of TINCR， MAFB， and KLF4 genes were significantly reduced （P < 0.001）， suggesting that TINCR may influence the differentiation of keratinocytes by regulating the expression of MAFB transcription factor and KLF4 differentiation-related genes. Furthermore， immunohistochemical results indicated that the expression of KLF4 protein was significantly elevated in psoriasis tissues compared to normal skin tissues， suggesting that KLF4 plays an important role in the pathogenesis of psoriasis. Conclusions The TINCR-MAF：MAFB transcription factor network may participate in the occurrence and development of psoriasis by affecting the proliferation and differentiation of keratinocytes. This finding provides a new perspective on the pathogenesis of psoriasis and potential targets for future therapeutic strategies.

Key words: psoriasis, TINCR, MAF, MAFB, KLF4

CLC Number:

R751

Jinfen ZHENG,Cuiping SHI,Yunxia LING,Dehua ZHANG,Qianyu ZHAI,Lijia ZHU,Doukou JIANG,Xiaohong WANG,Yonghui. LAI. Effect of TINCR⁃MAF： MAFB transcription factor network on proliferation and differentiation of human kerathnocytes[J]. The Journal of Practical Medicine, 2025, 41(4): 509-514.

Figures/Tables 6

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References 21

1	郑锦芬，洪福昌，杨帆，等. CAVEOLIN-2在寻常型银屑病患者皮肤组织中的表达特征［J］. 实用医学杂志， 2016， 32（11）：1791-1794. doi:10.3969/j.issn.1006-5725.2016.11.019 doi: 10.3969/j.issn.1006-5725.2016.11.019
2	GHAFOURI-FARD S， MOGHADAM M H B， SHOOREI H， et al. The impact of non-coding RNAs on normal stem cells［J］. Biomed Pharmacother，2021， 142：112050. doi:10.1016/j.biopha.2021.112050 doi: 10.1016/j.biopha.2021.112050
3	DERRIEN T， JOHNSON R， BUSSOTTI G， et al. The GENCODE v7 catalog of human long noncoding RNAs： analysis of their gene structure， evolution， and expression［J］. Genome Res，2012， 22（9）：1775-1789. doi:10.1101/gr.132159.111 doi: 10.1101/gr.132159.111
4	FUJINO M， OJIMA M， TAKAHASHI S. Exploring Large MAF Transcription Factors：Functions， Pathology， and Mouse Models with Point Mutations［J］. Genes （Basel），2023， 14（10）：1883. doi:10.3390/genes14101883 doi: 10.3390/genes14101883
5	MIYAI M， TSUNEKAGE Y， SAITO M， et al. Ectopic expression of the transcription factor MafB in basal keratinocytes induces hyperproliferation and perturbs epidermal homeostasis［J］. Exp Dermatol，2017， 26（11）：1039-1045. doi:10.1111/exd.13364 doi: 10.1111/exd.13364
6	OGATA A， SHIMIZU T， ABE R， et al. Expression of c-maf and mafB genes in the skin during rat embryonic development［J］. Acta Histochem， 2004， 106（1）：65-67. doi:10.1016/j.acthis.2003.10.001 doi: 10.1016/j.acthis.2003.10.001
7	GHALEB A M， YANG V W. Krüppel-like factor 4 （KLF4）： What we currently know［J］. Gene， 2017， 611：27-37. doi:10.1016/j.gene.2017.02.025 doi: 10.1016/j.gene.2017.02.025
8	艾民，张清华，蒋知新，等. 利用SOX2、Klf4、OCt4、c-Myc基因将脐带基质间充质细胞编程为多潜能干细胞［J］. 实用医学杂志， 2011， 27（21）：3825-3827.
9	袁源，钟竑. 诱导多能干细胞的研究进展［J］. 实用医学杂志， 2010， 26（6）：897-899.
10	LABOTT A T， LOPEZ-PAJARES V. Epidermal differentiation gene regulatory networks controlled by MAF and MAFB［J］. Cell Cycle， 2016， 15（11）：1405-1409. doi:10.1080/15384101.2016.1172148 doi: 10.1080/15384101.2016.1172148
11	LOPEZ-PAJARES V， QU K， ZHANG J， et al. A LncRNA-MAF：MAFB transcription factor network regulates epidermal differentiation［J］. Dev Cell， 2015， 32（6）：693-706. doi:10.1016/j.devcel.2015.01.028 doi: 10.1016/j.devcel.2015.01.028
12	中华医学会皮肤性病学分会银屑病专业委员会.中国银屑病诊疗指南（2023版）［J］.中华皮肤科杂志， 2023， 56（7）：573-625.
13	KSHIRSAGAR S J， ADHAV P S， LADDHA U D， et al. Navigating psoriasis： From immune mechanisms to natural healing approaches［J］. Int Immunopharmacol， 2025， 144：113626. doi:10.1016/j.intimp.2024.113626 doi: 10.1016/j.intimp.2024.113626
14	吴维维，韩君雅，张艳，等. 反射式共聚焦显微镜在司库奇尤单抗治疗中重度斑块型银屑病疗效评估中的价值［J］. 实用医学杂志， 2022， 38（24）： 3072-3076.
15	沈嘉庆，刘毅. 酪氨酸激酶2抑制剂治疗斑块型银屑病机制与临床研究进展［J］. 中国临床药理学与治疗学， 2023， 28（3）： 323-330.
16	李思彤，王傲，白彦萍，等. 银屑病中滤泡性辅助性T细胞及IL-21对HaCaT细胞增殖及细胞周期的影响［J］. 实用医学杂志， 2023， 39（18）： 2342-2348. doi:10.3969/j.issn.1006-5725.2023.18.010 doi: 10.3969/j.issn.1006-5725.2023.18.010
17	张晓丽，刘毅. 瞬时受体电位离子通道与银屑病的研究进展［J］. 中国临床药理学与治疗学， 2021， 26（4）： 469-473. doi:10.12092/j.issn.1009-2501.2021.04.016 doi: 10.12092/j.issn.1009-2501.2021.04.016
18	TALIERCIO M， LEBWOHL M. Psoriasis Comorbidities and Their Treatment Impact［J］. Dermatol Clin， 2024， 42（3）：405-416. doi:10.1016/j.det.2024.02.007 doi: 10.1016/j.det.2024.02.007
19	邰宇，张子璇，张玲玲. 银屑病关节炎治疗进展［J］. 中国临床药理学与治疗学， 2020， 25（12）： 1395-1407.
20	MARTIN A， IBRAHEIM M K， GUPTA R， et al. Innovations in Psoriasis［J］. Dermatol Clin， 2025， 43（1）：1-9. doi:10.1016/j.det.2024.08.001 doi: 10.1016/j.det.2024.08.001
21	MIYAI M， HAMADA M， MORIGUCHI T， et al. Transcription Factor MafB Coordinates Epidermal Keratinocyte Differentiation［J］. J Invest Dermatol， 2016， 136（9）：1848-1857. doi:10.1016/j.jid.2016.05.088 doi: 10.1016/j.jid.2016.05.088

名称	序列信息
名称	Sense（5′‐3′）（包括overhangs）	Antisense（5′‐3′）（包括overhangs）
siRNA?58	GCUGGAAGCGCUACCACAUTT	AUGUGGUAGCGCUUCCAGCTT
siRNA?217	UGGACGACCACCAGACGGUTT	ACCGUCUGGUGGUCGUCCATT
siRNA?169	AGGGCGUGAGCUCCUGGAATT	UUCCAGGAGCUCACGCCCUTT
siRNA?NC	UUCUCCGAACGUGUCACGUTT	ACGUGACACGUUCGGAGAATT

组别	TINCR相对表达量
F值 P值	639.41 < 0.001
control组	1.00 ± 0.03
siRNA?NC组	0.98 ± 0.04
siRNA?58组	0.27 ± 0.00^?#
siRNA?217组	0.37 ± 0.01^?#
siRNA?169组	0.48 ± 0.01^?#

时间		OD值（450 nm）		F值	P值
时间	control组	siRNA?NC组	siRNA?58组	F值	P值
0 h	0.226 ± 0.011	0.219 ± 0.013	0.202 ± 0.099	10.392	0.001
24 h	0.471 ± 0.036	0.424 ± 0.034	0.288 ± 0.023^?#	81.195	< 0.001
48 h	1.115 ± 0.053	1.054 ± 0.064	0.881 ± 0.031^?#	51.019	< 0.001
72 h	1.621 ± 0.068	1.522 ± 0.081^?	1.105 ± 0.042^?#	156.153	< 0.001

基因名称		相对表达量		F值	P值
基因名称	control组	siRNA?NC组	siRNA?58组	F值	P值
TINCR	0.936 ± 0.121	0.950 ± 0.112	0.255 ± 0.051^?	142.649	< 0.001
MAFB	0.978 ± 0.137	1.004 ± 0.083	0.548 ± 0.141^?	39.071	< 0.001
KLF4	0.962 ± 0.111	1.009 ± 0.119	0.574 ± 0.110^?	39.953	< 0.001

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Effect of TINCR⁃MAF： MAFB transcription factor network on proliferation and differentiation of human kerathnocytes

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