The Associations of Single Nucleotide Polymorphisms of the COL3A1, COL6A5, and COL8A1 Genes with Atopic Dermatitis

Szalus, Krzysztof; Zysk, Weronika; Gleń, Jolanta; Zabłotna, Monika; Nowicki, Roman; Trzeciak, Magdalena

doi:10.3390/jpm13040661

Cited by 5 publications

(3 citation statements)

References 34 publications

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“…We can hypothesize that being expressed close to the skin barrier, a change in COL6A5 structure may affect the permeability of the skin. This is an interesting hypothesis to follow, considering the association of COL6A5 polymorphisms with atopic dermatitis (Szalus et al 2023) and an additional hypothesis based on COL6A5 + dermis broblasts contributing to skin in ammation (Li et al 2023).…”

Section: Discussionmentioning

confidence: 99%

The COL6A5-p.Glu2272* mutation induces chronic itch in mice

Rasheed,

Birling,

Lauria

et al. 2024

Mamm Genome

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Pruritus is a common irritating sensation that provokes the desire to scratch. Environmental and genetic factors, altering barrier skin dysfunction, or hypersensitivity of sensory nerves, contribute to the onset of pruritus. However, the itch can become a major burden when it becomes chronic, like in neuropathic itch. The rare Collagen VI alpha 5 (COL6A5) gene variant p.Glu2272* was recently identi ed in two families and an independent patient with chronic neuropathic itch. These patients showed reduced COL6A5 expression in the skin and normal skin morphology. However, little progress has been made until now toward understanding the relationships between this mutation and chronic itch. Therefore, we developed the rst mouse model that recapitulates COL6A5-p.Glu2272* mutation using the CRISPR-Cas technology and characterized this new mouse model. The mutant mRNA, measured by RT-ddPCR, was expressed at normal levels in dorsal root ganglia and decreased in skin. The functional exploration showed changes in the behavior of control individuals kept with mutant carriers and con rmed the effect in the mutant mice with some sex dysmorphology. Spontaneous scratching was detected in male and female mutants, with increased anxiety-like behavior in female mutants and despair-like behavior in sex-grouped mutants. These results suggest that the COL6A5-p.Glu2272* mutation found in patients contributes to chronic itch and probably induces additional behavioral changes. The COL6A5-p.Glu2272* mouse model could elucidate the pathophysiological mechanisms underlying COL6A5 role in neuropathic itch and help identify potential new therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

The COL6A5-p.Glu2272* mutation induces chronic itch in mice

Rasheed,

Birling,

Lauria

et al. 2024

Mamm Genome

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“…Notably, prior investigations have unveiled the profound impact of collagen peptide and vitamin C derivative co-treatment on upregulating COL1A1 and Has2 expression, thereby averting skin thinning (Shibuya et al, 2014). Furthermore, single nucleotide polymorphisms within the COL3A1 and COL6A5 genes have been associated with atopic dermatitis, revealing distinct genotype-phenotype relationships (Szalus et al, 2023). These genetic variations within these collagen-related genes may exert substantial influence on collagen expression, structure, and function, thereby modulating the pathogenesis and clinical manifestations of atopic dermatitis (Söderhäll et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive transcriptomic analysis unveils the interplay of mRNA and LncRNA expression in shaping collagen organization and skin development in Dezhou donkeys

Wang,

Peng,

Liang

et al. 2024

Front. Genet.

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The primary focus of donkey hide gelatin processing lies in the dermal layer of donkey hide due to its abundant collagen content. However, the molecular mechanism involved in collagen organization and skin development in donkey skin tissue across various developmental stages remains incomplete. The current study aims to investigate the transcriptomic screening of lncRNAs and mRNA associated with skin development and collagen organization across different ages in Dezhou donkeys’ skin. In the pursuit of this objective, we used nine skin tissue samples obtained from Dezhou donkeys at various ages including 8-month fetal stage, followed by 2 and 8 years. RNA-seq analysis was performed for the transcriptomic profiling of differentially expressed genes (DEGs) and lncRNAs associated with skin development in different age groups. Our investigation revealed the presence of 6,582, 6,455, and 405 differentially expressed genes and 654, 789, and 29 differentially expressed LncRNAs within the skin tissues of Dezhou donkeys when comparing young donkeys (YD) vs. middle-aged donkeys (MD), YD vs. old donkeys (OD), and MD vs. OD, respectively. Furthermore, we identified Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type III Alpha 1 Chain (COL3A1), and Collagen Type VI Alpha 5 Chain (COL6A5) as key genes involved in collagen synthesis, with COL1A1 being subject to cis-regulation by several differentially expressed LncRNAs, including ENSEAST00005041187, ENSEAST00005038497, and MSTRG.17248.1, among others. Interestingly, collagen organizational and skin development linked pathways including Protein digestion and absorption, metabolic pathways, Phosphatidylinositol 3-Kinase-Protein Kinase B signaling pathway (PI3K-Akt signaling pathway), Extracellular Matrix-Receptor Interaction (ECM-receptor interaction), and Relaxin signaling were also reported across different age groups in Dezhou donkey skin. These findings enhance our comprehension of the molecular mechanisms underlying Dezhou donkey skin development and collagen biosynthesis and organization, thus furnishing a solid theoretical foundation for future research endeavors in this domain.

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“…COL6A5, also present in other locations of individuals with allergic conditions, has been identified as a gene involved in the development of AD ( 69 ). The potential contribution of COL6A5 in AD may be attributed to the creation of unstable heterotrimers, resulting in abnormal fibroblast adhesion and barrier dysfunction ( 70 ). COL18A1 can strongly bind to the ECM component and potentially disrupt and destabilize the ECM in AD lesions.…”

Section: Activated Fibroblasts-entangled Crosstalk In Non-fibrotic In...mentioning

confidence: 99%

New insight into the role of fibroblasts in the epithelial immune microenvironment in the single-cell era

Wang,

Kou

et al. 2023

Front. Immunol.

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The skin is exposed to environmental challenges and contains heterogeneous cell populations such as epithelial cells, stromal cells, and skin-resident immune cells. As the most abundant type of stromal cells, fibroblasts have been historically considered silent observers in the immune responses of the cutaneous epithelial immune microenvironment (EIME), with little research conducted on their heterogeneity and immune-related functions. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have overcome the limitations of bulk RNA sequencing and help recognize the functional and spatial heterogeneity of fibroblasts, as well as their crosstalk with other types of cells in the cutaneous EIME. Recently, emerging single-cell sequencing data have demonstrated that fibroblasts notably participate in the immune responses of the EIME and impact the initiation and progression of inflammatory skin diseases. Here, we summarize the latest advances in the role of fibroblasts in the cutaneous EIME of inflammatory skin diseases and discuss the distinct functions and molecular mechanisms of activated fibroblasts in fibrotic skin diseases and non-fibrotic inflammatory skin diseases. This review help unveil the multiple roles of fibroblasts in the cutaneous EIME and offer new promising therapeutic strategies for the management of inflammatory skin diseases by targeting fibroblasts or the fibroblast-centered EIME.

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The Associations of Single Nucleotide Polymorphisms of the COL3A1, COL6A5, and COL8A1 Genes with Atopic Dermatitis

Cited by 5 publications

References 34 publications

The COL6A5-p.Glu2272* mutation induces chronic itch in mice

The COL6A5-p.Glu2272* mutation induces chronic itch in mice

Comprehensive transcriptomic analysis unveils the interplay of mRNA and LncRNA expression in shaping collagen organization and skin development in Dezhou donkeys

New insight into the role of fibroblasts in the epithelial immune microenvironment in the single-cell era

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