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Molecular effects of different TRPV3 Mutations

ABSTRACT: To understand the impact of dysfunctional TRPV3 on keratinocyte proliferation and differentiation, we conducted transcriptomic analysis on cells that express cloned different TRPV3 mutations identified in focal palmoplantar keratoderma (FPPK) patients and identified a number of perturbed pathways associated with epidermal cells construction and development. We also analyzed the molecular changes of skin biopsy samples from patients. Our data suggests that TRPV3 dysfunction inhibits keratinocyte differentiation, actives apoptosis pathway resulted in cell death, and disturbs the balance between keratinocyte proliferation and differentiation processes in the skin.

ORGANISM(S): Homo sapiens

PROVIDER: GSE71236 | GEO | 2015/12/31

SECONDARY ACCESSION(S): PRJNA290647

REPOSITORIES: GEO

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Molecular effects of different TRPV3 Mutations

Project description:To understand the impact of dysfunctional TRPV3 on keratinocyte proliferation and differentiation, we conducted transcriptomic analysis on cells that express cloned different TRPV3 mutations identified in focal palmoplantar keratoderma (FPPK) patients and identified a number of perturbed pathways associated with epidermal cells construction and development. We also analyzed the molecular changes of skin biopsy samples from patients. Our data suggests that TRPV3 dysfunction inhibits keratinocyte differentiation, actives apoptosis pathway resulted in cell death, and disturbs the balance between keratinocyte proliferation and differentiation processes in the skin. To explore the functional impact of the different TRPV3 mutations on cells, we cloned the wild type and mutant TRPV3 clones into expression vector. The wild-type human TRPV3 gene was amplified from cDNA made from a mixture of human tissue total RNA and cloned into pcDNA3.1 (Life Technologies, Carlsbad, CA). The accuracy of the cloned sequence was checked with Sanger sequencing. Quick Change II XL site-directed mutagenesis kit (Agilent, Santa Clara, CA) was used to introduce sequence changes corresponding to mutations observed in patients. The HEK293T cells were transfected using Lipofectamine 2000 (Life Technologies, Carlsbad, CA) according to the manufacturerâs instructions. Cells were also transfected with the same plasmid without insert as control.

2015-12-31 | E-GEOD-71236 | biostudies-arrayexpress

Gene expression signatures of HaCaT cell lines transfected with mutant TRPV3

Project description:We identified a number of affected pathways through transcriptome analysis on the skin biopsy samples of the FPPK patients. Our findings suggest that TRPV3 dysfunction may increase apoptotic activity, inhibit keratinocyte differentiation and disturb the intricate balance between proliferation and differentiation state of keratinocytes in the skin. To understand the effect of TRPV3 mutation, transcriptome of HaCaT cell lines transfected with mutant TRPV3 were profiled in time-course manner (16, 24 and 40hr).

2013-12-24 | E-GEOD-53615 | biostudies-arrayexpress

Gene expression signatures of 293T cell lines transfected with mutant TRPV3

Project description:We identified a number of affected pathways through transcriptome analysis on the skin biopsy samples of the FPPK patients. Our findings suggest that TRPV3 dysfunction may increase apoptotic activity, inhibit keratinocyte differentiation and disturb the intricate balance between proliferation and differentiation state of keratinocytes in the skin. To understand the effect of TRPV3 mutation, transcriptome of 293T cell lines transfected with mutant TRPV3 were profiled in time-course manner (16, 24 and 40hr).

2013-12-24 | E-GEOD-53614 | biostudies-arrayexpress

Gene expression signatures of HaCaT cell lines transfected with mutant TRPV3

2013-12-24 | GSE53615 | GEO

Gene expression signatures of 293T cell lines transfected with mutant TRPV3

2013-12-24 | GSE53614 | GEO

Gene expression signatures in the skin of focal palmoplantar keratoderma (FPPK) patients

2013-12-24 | GSE53613 | GEO

Gene expression signatures in the skin of focal palmoplantar keratoderma (FPPK) patients

Project description:We identified a number of affected pathways through transcriptome analysis on the skin biopsy samples of the FPPK patients. Our findings suggest that TRPV3 dysfunction may increase apoptotic activity, inhibit keratinocyte differentiation and disturb the intricate balance between proliferation and differentiation state of keratinocytes in the skin. From a 37-year-old Chinese male (II-7) and his 12-year-old son (III-7), biopsies from unaffected and affected skin tissues were obtained and their transcriptome profiles were analyzed in order to identify molecular changes related with the pathology of FPPK.

2013-12-24 | E-GEOD-53613 | biostudies-arrayexpress

TRPV3 mediates Propionibacterium acnes-induced chemotaxis and inflammation in sebocytes

Project description:TRPV3 is highly expressed in human skin and is involved in the development of inflammatory dermatoses. However, it remains unclear whether TRPV3 influences inflammation in human sebaceous glands and its role in the pathogenesis of acne. Here, we showed that TRPV3 expression was increased in the sebaceous glands of facial acne lesions and acne-like mice. TRPV3 increased the secretion of pro-inflammatory cytokines and chemokines in human SZ95 sebocytes, as well as the chemotaxis of neutrophils, which were the major immune cells found in acne lesions. We demonstrated that P.acnes promoted TRPV3 expression through regulating lipid profile especially upregulated arachidonic acid levels in human sebocytes. TRPV3 further upregulated TLR2 expression by promoting transcriptional factor p-FOSL1 expression and its binding to the TLR2 promoter, leading to downstream NF-κB signaling activation. Importantly, either genetic silencing or pharmacological inhibition of TRPV3 alleviated acne-like inflammation in mice, showing reduced acne-characteristic cytokines and chemokines production and neutrophil infiltration by inhibiting the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebocytes inflammation, which was involved in the development of acne, indicating that TRPV3 is a potential therapeutic target for acne and other disorders of the pilosebaceous unit.

2023-10-13 | GSE245001 | GEO

Differential cell composition and split epidermal differentiation in human palm, sole, and hip skin

Project description:Palmoplantar skin is structurally and functionally unique, but the transcriptional programs driving this specialization are unknown. Here, we exploit bulk and single-cell RNA-sequencing of human palm, sole, and hip skin to describe the distinguishing characteristics of palmoplantar and non-palmoplantar skin while also uncovering previously unappreciated differences between palmar and plantar sites. Our approach reveals downregulation of diverse immunological processes and decreased immune cell populations in palmoplantar skin, highlighting an altered immune environment in the skin of the palms and soles. Further, we identify specific palmoplantar and non-palmoplantar fibroblast populations that appear to orchestrate key differences in cell-cell communication in palm, sole, and hip. Dedicated analysis of epidermal keratinocytes highlights major differences in basal cell fraction among the three sites and validates the presence of a more differentiated, cycling basal population. Finally, our data demonstrate the existence of two spinous keratinocyte populations that constitute two parallel, site-selective epidermal differentiation trajectories. Together, these results provide a deep characterization of the highly adapted palmoplantar skin and contribute new insights into the fundamental biology of human skin.

2023-01-05 | GSE193101 | GEO

scRNA-seq reveals differences in cell states and cell types between human hip, palm, and sole skin

Project description:Palmoplantar skin is structurally and functionally unique, but the transcriptional programs driving this specialization are unknown. Here, we exploit single-cell RNA-sequencing of human palm, sole, and hip skin to describe the distinguishing characteristics of palmoplantar and non-palmoplantar skin while also uncovering previously unappreciated differences between palmar and plantar sites. Our approach reveals downregulation of diverse immunological processes and decreased immune cell populations in palmoplantar skin, highlighting an altered immune environment in the skin of the palms and soles. Further, we identify specific palmoplantar and non-palmoplantar fibroblast populations that appear to orchestrate key differences in cell-cell communication in palm, sole, and hip. Dedicated analysis of epidermal keratinocytes highlights major differences in basal cell fraction among the three sites and validates the presence of a more differentiated, cycling basal population. Finally, our data demonstrate the existence of two spinous keratinocyte populations that constitute two parallel, site-selective epidermal differentiation trajectories. Together, these results provide a deep characterization of the highly adapted palmoplantar skin and contribute new insights into the fundamental biology of human skin.

2023-01-11 | GSE202352 | GEO

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