Knockout of the Arp2/3 complex in epidermis causes a psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2

Kammen, Rob van der; Song, Ji Ying; Rink, Iris de; Janssen, Hans; Madonna, Stefania; Scarponi, Claudia; Albanesi, Cristina; Brugman, Wim; Innocenti, Metello

doi:10.1242/dev.156323

Cited by 34 publications

(30 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Disrupting the metazoan ARP2/3 complex also tends to result in tissue-or organ-level problems rather than cellular lethality (e.g. Di Nardo et al, 2005;van der Kammen et al, 2017). In plants, the ARP2/3 complex appears to be needed for proper cell morphogenesis and development but not for cell viability.…”

Section: Discussionmentioning

confidence: 99%

Division of Labor Between Two Actin Nucleators—the Formin FH1 and the ARP2/3 Complex—in Arabidopsis Epidermal Cell Morphogenesis

et al. 2020

View full text Add to dashboard Cite

The ARP2/3 complex and formins are the only known plant actin nucleators. Besides their actin-related functions, both systems also modulate microtubule organization and dynamics. Loss of the main housekeeping Arabidopsis thaliana Class I membranetargeted formin FH1 (At3g25500) is known to increase cotyledon pavement cell lobing, while mutations affecting ARP2/3 subunits exhibit an opposite effect. Here we examine the role of FH1 and the ARP2/3 complex subunit ARPC5 (At4g01710) in epidermal cell morphogenesis with focus on pavement cells and trichomes using a model system of single fh1 and arpc5, as well as double fh1 arpc5 mutants. While cotyledon pavement cell shape in double mutants mostly resembled single arpc5 mutants, analysis of true leaf epidermal morphology, as well as actin and microtubule organization and dynamics, revealed a more complex relationship between the two systems and similar, rather than antagonistic, effects on some parameters. Both fh1 and arpc5 mutations increased actin network density and increased cell shape complexity in pavement cells and trichomes of first true leaves, in contrast to cotyledons. Thus, while the two actin nucleation systems have complementary roles in some aspects of cell morphogenesis in cotyledon pavement cells, they may act in parallel in other cell types and developmental stages.

show abstract

Section: Discussionmentioning

confidence: 99%

Division of Labor Between Two Actin Nucleators—the Formin FH1 and the ARP2/3 Complex—in Arabidopsis Epidermal Cell Morphogenesis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Through this approach, potential susceptibility genes may be found or suspected genes experimentally validated by assessing the transcriptomic profile of in vitro gene edited cells [135,206]. In a similar way, the role of the cytoskeleton regulator Arp2/3 complex was evaluated by transcriptomics of an Arpc4 knockout mouse strain to investigate psoriasis-specific features [207]. In the field of psoriasis research, Imiquimod (IMQ)-induced dermatitis is a widely used murine model which mainly acts via TLR7/8 agonism [208] and largely depends on IL-17 signaling [209][210][211].…”

Section: Validating Disease Modelsmentioning

confidence: 99%

Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis

Schwingen

Kaplan

Kurschus

2020

IJMS

View full text Add to dashboard Cite

During the last decades, high-throughput assessment of gene expression in patient tissues using microarray technology or RNA-Seq took center stage in clinical research. Insights into the diversity and frequency of transcripts in healthy and diseased conditions provide valuable information on the cellular status in the respective tissues. Growing with the technique, the bioinformatic analysis toolkit reveals biologically relevant pathways which assist in understanding basic pathophysiological mechanisms. Conventional classification systems of inflammatory skin diseases rely on descriptive assessments by pathologists. In contrast to this, molecular profiling may uncover previously unknown disease classifying features. Thereby, treatments and prognostics of patients may be improved. Furthermore, disease models in basic research in comparison to the human disease can be directly validated. The aim of this article is not only to provide the reader with information on the opportunities of these techniques, but to outline potential pitfalls and technical limitations as well. Major published findings are briefly discussed to provide a broad overview on the current findings in transcriptomics in inflammatory skin diseases.

show abstract

“…3,[6][7][8]16 In this study, the relationship between ARPC4 expression and the oncogenicity of bladder cancer was determined. It may therefore represent a promising biomarker and therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

ARPC4 promotes bladder cancer cell invasion and is associated with lymph node metastasis

et al. 2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

The significance of actin‐related protein 2/3 complex subunit 4 (ARPC4) expression in bladder cancer, and its potential role in the invasion and migration of bladder cancer cells, has yet to be determined. This study was to identify the correlation between ARPC4 and lymph node metastasis, and to determine the role of ARPC4 in the invasive migration of T24 bladder cancer cells. One hundred and ninety‐eight bladder cancer tissues and 40 normal bladder and lymph node tissues were examined. Tissue microarrays were constructed and subjected to immunohistochemical stating for ARPC4. Multiple logistic analysis was used to determine risk factors associated with bladder cancer metastasis. ARPC4 expression in T24 bladder cancer cells was suppressed using small interfering RNA and changes in protein levels were determined by Western blot analysis. The proliferation of bladder cancer cells after knocking down of ARPC4 was determined by cell counting kit‐8. The effects of ARPC4 knockdown on T24 cell invasion and migration was determined using transwell and wound healing assays. Immunofluorescence analysis was performed to examine changes in pseudopodia formation and actin cytoskeleton structure. The expression of ARPC4 was elevated in bladder cancer tissues than normal tissues (84.3% vs 27.5%, P < 0.001). The multivariate logistic analysis demonstrated that the level of ARPC4, as a risk factor, was correlated with lymphatic metastasis (P < 0.05). ARPC4 knockdown attenuated proliferation, migration, invasion, and pseudopodia formation in T24 cells. ARPC4 expression, as a risk factor, is associated with lymphatic metastasis and is upregulated in bladder cancer tissues in comparison with normal tissues. Inhibition of ARPC4 expression significantly attenuates the proliferation, migration, and invasion of bladder cancer cell, possibly due to defects in pseudopodia formation.

show abstract

Knockout of the Arp2/3 complex in epidermis causes a psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2

Cited by 34 publications

References 62 publications

Division of Labor Between Two Actin Nucleators—the Formin FH1 and the ARP2/3 Complex—in Arabidopsis Epidermal Cell Morphogenesis

Division of Labor Between Two Actin Nucleators—the Formin FH1 and the ARP2/3 Complex—in Arabidopsis Epidermal Cell Morphogenesis

Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis

ARPC4 promotes bladder cancer cell invasion and is associated with lymph node metastasis

Contact Info

Product

Resources

About