Phospholipase Cγ1 is required for normal irritant contact dermatitis responses and sebaceous gland homeostasis

Nakamura, Yoshikazu; Kanemaru, Kaori; Toyoda, Chiho; Jang, Hyun Jun; Suh, Pann Ghill; Fukami, Kiyoko

doi:10.1111/exd.14009

Cited by 2 publications

(2 citation statements)

References 34 publications

(47 reference statements)

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“…It is reported that EGFR plays a crucial role in controlling the processes of both proliferation and differentiation in the epidermis. 28 Recent studies have revealed that EGFR regulates a complex signaling network within cells and its role in regulating cellular metabolism is emerging as one of its important functions. 29 Among the various metabolic pathways, glycolysis and mitochondrial metabolism are the main pathways that support cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Study on the Key Genes and Molecular Mechanisms of IL-27 Promoting Keratinocytes Proliferation Based on Transcriptome Sequencing

Wu¹,

Yang²,

Xu³

et al. 2023

CCID

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Background IL-27 involves psoriasis pathogenesis potentially by promoting excessive keratinocyte proliferation. However, the underlying mechanisms remain unclear. This study aims to explore the key genes and molecular mechanisms of IL-27-induced keratinocyte proliferation. Methods Primary keratinocytes and immortalized human keratinocyte HaCaT cells were treated with different concentrations of IL-27 for 24 h and 48 h respectively. CCK-8 assay was used to detect cell viability and Western blot was used to detect the expression of CyclinE and CyclinB1. Primary keratinocytes and HaCaT cells were treated with IL-27, and their differentially expressed (DE) genes were obtained by transcriptome sequencing. Then Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed to predict related pathways, and the long non-coding RNA-microRNA-messenger RNA network and protein-protein interaction network were constructed to screen key genes. Biochemical experiments were performed to assess the content of glucose (Glu), lactic acid (LA), and ATP. Flow cytometry and Mito-Tracker Green staining were used to detect mitochondrial membrane potential and the number of mitochondria respectively. Western blot was performed to assess the expression of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), phosphoglycerate kinase 1 (PGK1), phosphorylated dynamin-related protein 1 (p-DRP1) (s637) and mitofusin 2 (MFN2). Results IL-27 concentration-dependently increased keratinocyte viability and the expression of CyclinE and CyclinB1. Bioinformatics analysis showed that the enriched pathways of DE genes were closely associated with cellular metabolism. miR-7-5p, EGFR, PRKCB, PLCB1 and CALM3 were key genes. IL-27 increased the content of LA, mitochondrial membrane potential, and the expression of GLUT1, HK2, LDHA, PGK1, p-DRP1 (s637), and MFN2, accompanied by decreased contents of Glu and ATP (P<0.001). Conclusion IL-27 potentially promotes keratinocyte proliferation by enhancing glycolysis, mitochondrial function, and mitochondrial fusion. The findings of this study may be conducive to revealing the role of IL-27 in the pathogenesis of psoriasis.

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Section: Discussionmentioning

confidence: 99%

Study on the Key Genes and Molecular Mechanisms of IL-27 Promoting Keratinocytes Proliferation Based on Transcriptome Sequencing

Wu¹,

Yang²,

Xu³

et al. 2023

CCID

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“…Highlighting in vivo mouse model studies are recent works on hair follicle development and growth 1‐5 and wound healing 6‐8 . Further, studies in animal models often help to elucidate aspects of disease pathogenesis, and mouse models are used to investigate mechanisms of human skin conditions such as atopic dermatitis, 9‐13 contact dermatitis, 14‐16 psoriasis, 17,18 rosacea 19 and squamous cell carcinoma 20 to name a few.…”

Section: Bridging the Gap Between “Simplicity” Of In Vitro And Complementioning

confidence: 99%

Fostering a healthy culture: Biological relevance of in vitro and ex vivo skin models

Atwood

Plikus

2021

Experimental Dermatology

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The field of experimental dermatology research has dramatically benefited from the insights yielded by in vivo studies on animal models. Indeed, much of our understanding of the mechanisms that regulate embryonic skin development, adult skin homeostasis and physiological skin responses to stress, such as wound healing, has been educated by studies conducted in animal models, including mutant mice. These works become commonly published on the pages of Experimental Dermatology and, in fact, represent one of the core interests of the journal. Highlighting in vivo mouse model studies are recent works on hair follicle development and growth 1-5 and wound healing. 6-8 Further, studies in animal models often help to elucidate aspects of disease pathogenesis, and mouse models are used to investigate mechanisms of human skin conditions such as atopic dermatitis, 9-13 contact dermatitis, 14-16 psoriasis, 17,18 rosacea 19 and squamous cell carcinoma 20 to name a few. On the other hand, not all human skin diseases or aspects of human skin physiology can be reliably modelled in rodents. This is not surprising, considering that humans and rodents are separated by an estimated 96 million years of evolution. 21 Addressing this fact, many studies are being conducted on patient-derived primary skin cells, including human keratinocytes, 22-25 melanocytes, 26-30 fibroblasts 31-34 and cell co-cultures. 35-37 However, typical in vitro culture conditions fail to replicate and, in fact, do not come close to imitating the biomechanical and biochemical complexity of the microenvironment in which cells exist and to which they respond to in native tissues. Further, ingredients in commonly used cell culture media and the two-dimensional constraints of growth on plastic result in cells being exposed to a lot of artificial cues, to which they adapt but also prominently alter their gene expression profile and functional activities in the process. Therefore, behaviours displayed by skin cells in twodimensional cultures need to be comprehensively validated under more native-like conditions in order to be deemed biologically and physiologically relevant. Helping to bridge the gap, threedimensional (3D) organotypic cultures and organ culture techniques have long been a highly instructive tool for investigating complex, tissue-level behaviours by skin cells.

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Phospholipase Cγ1 is required for normal irritant contact dermatitis responses and sebaceous gland homeostasis

Cited by 2 publications

References 34 publications

Study on the Key Genes and Molecular Mechanisms of IL-27 Promoting Keratinocytes Proliferation Based on Transcriptome Sequencing

Study on the Key Genes and Molecular Mechanisms of IL-27 Promoting Keratinocytes Proliferation Based on Transcriptome Sequencing

Fostering a healthy culture: Biological relevance of in vitro and ex vivo skin models

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