Modulation of Keratinocyte Proliferation by Skin Innervation

Psoriasis is a chronic inflammatory skin disorder which affects more than 3% of the population worldwide and is characterized histopathologically by proliferative imbalance and abnormal differentiation of epidermal keratinocytes and inflammatory infiltration. Hence, loss of regulation in keratinocyte proliferation and differentiation makes it a typical pathophysiological phenomenon in psoriasis manifestation. Traditionally, herbal products used in treating psoriasis have shown promising effects in several clinical studies with relatively fewer adverse effects, higher remission and lower recurrence rates. In our previous study, the polyherbal formulation of InnoVision’s test material was found to induce AQP-3 expression in keratinocyte cell line. In the present study, we screened the study material for its anti-proliferative properties using cultured human HACAT keratinocyte cell model. Our experimental results suggest that InnoVision’s Psoriderm Cream is a promising source which can be effectively used as an herb-based topical agent for psoriasis treatment. Evidence is provided that inhibition of keratinocyte proliferation and improving skin hydration via induction of aquaporin-3 stimulation is the possible underlying mechanism for the observed anti-psoriatic action of study material.

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Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure

International Journal of Molecular Sciences ◽

10.3390/ijms20153679 ◽

2019 ◽

Vol 20 (15) ◽

pp. 3679 ◽

Cited By ~ 3

Author(s):

Lin Chen ◽

Alyne Simões ◽

Zujian Chen ◽

Yan Zhao ◽

Xinming Wu ◽

...

Keyword(s):

Wound Healing ◽

Oral Mucosa ◽

Wound Closure ◽

Expression Patterns ◽

Skin Wound ◽

Skin Wound Healing ◽

Specific Expression ◽

Keratinocyte Proliferation

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

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Transforming Growth Factor-β1 Inhibits Human Keratinocyte Proliferation by Upregulation of a Receptor-Type Tyrosine Phosphatase R-PTP-κ Gene Expression

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1996.1736 ◽

1996 ◽

Vol 228 (3) ◽

pp. 807-812 ◽

Cited By ~ 22

Author(s):

Young Yang ◽

Minchan Gil ◽

Si Myung Byun ◽

Inpyo Choi ◽

Kwang Ho Pyun ◽

...

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Transforming Growth Factor ◽

Tyrosine Phosphatase ◽

Transforming Growth Factor Β1 ◽

Receptor Type ◽

Keratinocyte Proliferation ◽

Human Keratinocyte

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The endoribonuclease N4BP1 prevents psoriasis by controlling both keratinocytes proliferation and neutrophil infiltration

Cell Death and Disease ◽

10.1038/s41419-021-03774-w ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Chenliang Gou ◽

Wenkai Ni ◽

Panpan Ma ◽

Fengbo Zhao ◽

Zhou Wang ◽

...

Keyword(s):

Physiological Role ◽

Neutrophil Infiltration ◽

Proper Function ◽

Psoriatic Skin ◽

Epidermal Keratinocytes ◽

Keratinocyte Proliferation ◽

Proliferation And Differentiation ◽

Long Time ◽

Chronic Skin ◽

Upregulated Genes

AbstractPsoriasis is a common chronic skin disease, characterized by abnormal interplay between hyperproliferative epidermal keratinocytes and self-reactive immune cells with not fully addressed molecular mechanism. N4BP1 (NEDD4-binding protein 1) is considered as an immune regulator for a long time but its physiological role is not determined yet. Here, we found that the expression of N4BP1 in skin was highest among all 54 tested tissues, and its expression was further upregulated in psoriatic skin. N4BP1-deficient mice exhibited normal grossly, but developed severe and prolonged IMQ-induced psoriasis-like disease comparing to controls. N4BP1 mainly expressed in keratinocytes and located on nucleus. Up- but not downregulated genes in N4BP1-deficient skin were specifically enriched in keratinocyte proliferation and differentiation. The proliferation of N4BP1-deficient primary keratinocytes was faster compared to that of controls. The upregulated genes upon ablation of N4BP1 were highly enriched in targets of AP-1 transcription factor. Knocking out N4BP1 resulted in upregulation of JunB and FosB, and conversely, overexpression of N4BP1 greatly reduced their expression. Furthermore, N4BP1 binds with JunB and FosB encoding mRNAs and greatly reduces their stability. In addition, with a high expression in neutrophils, N4BP1 limits survival of neutrophils in blood and infiltration of neutrophils in psoriatic skin by targeting CXCL1, CCL20, and S100A8. These findings demonstrate that N4BP1 controls the proper function of keratinocytes and neutrophils by negatively regulating JunB, FosB, and CXCL1, respectively, and that is critical for psoriasis prevention.

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