IQGAP3 Is an Important Mediator of Skin Inflammatory Diseases

被引:0
作者
Zolotarenko, Alena [1 ]
Bruskin, Sergey [1 ]
机构
[1] Russian Acad Sci, Vavilov Inst Gen Genet, Lab Funct Genom, Moscow 119991, Russia
基金
俄罗斯科学基金会;
关键词
keratinocytes; IQGAP3; RNAseq; inflammation; psoriasis; pathway analysis; proliferation; HEPATOCELLULAR-CARCINOMA; PROLIFERATION; PSORIASIS; ROLES;
D O I
10.3390/ijms25084545
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
IQGAP3 (IQ Motif Containing GTPase Activating Protein 3) is member of the IQGAP family of scaffold proteins, which are essential for assembling multiprotein complexes that coordinate various intracellular signaling pathways. Previous research has shown that IQGAP3 is overexpressed in psoriatic skin lesions. Given its involvement in processes like cell proliferation and chemokine signaling, we sought to explore its molecular role in driving the psoriatic phenotype of keratinocytes. By conducting transcriptome profiling of HaCaT keratinocytes, we identified numerous psoriasis-associated pathways that were affected when IQGAP3 was knocked down. These included alterations in NFkB signaling, EGFR signaling, activation of p38/MAPK and ERK1/ERK2, lipid metabolism, cytokine production, and the response to inflammatory cytokine stimulation. Real-time analysis further revealed changes in cell growth dynamics, including proliferation and wound healing. The balance between cell proliferation and apoptosis was altered, as were skin barrier functions and the production of IL-6 and IFN gamma. Despite these significant findings, the diversity of the alterations observed in the knockdown cells led us to conclude that IQGAP3 may not be the best target for the therapeutic inhibition to normalize the phenotype of keratinocytes in psoriasis.
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页数:16
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