Life before and beyond blistering: The role of collagen <scp>XVII</scp> in epidermal physiology

Natsuga, Ken; Watanabe, Mika; Nishie, Wataru; Shimizu, Hiroshi

doi:10.1111/exd.13550

Cited by 51 publications

(52 citation statements)

References 96 publications

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“…The presently used anti‐collagen α ‐1(XVII) chain antibody detects an intracellular domain of hemidesmosome‐bound collagen α ‐1(XVII) chain and not the earlier produced, cleaved and embedded ectodomain of the molecule (Figure S1). The collagen α ‐1(XVII) chain staining of apicolateral plasma membranes is, therefore, probably due to the presence of non‐hemidesmosomal collagen α ‐1(XVII) chain that might have other roles, like involvement in adherence junctions (30).…”

Section: Discussionmentioning

confidence: 99%

Composition of hemidesmosomes in basal keratinocytes of normal buccal mucosa and oral lichen planus

Schreurs

Balta

Karatsaidis

et al. 2020

European J Oral Sciences

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Oral lichen planus (OLP) is a chronic inflammatory disease displaying ultrastructural disturbances in epithelial hemidesmosomes. The expression of several key hemidesmosomal components in OLP as well as in normal buccal mucosa is, however, unknown. The aim of the study was therefore to examine intracellular and extracellular components involved in hemidesmosomal attachment, in OLP (n = 20) and in normal buccal mucosa (n = 10), by immunofluorescence. In normal buccal mucosa, laminin‐α3γ2, integrin‐α6β4, CD151, collagen α‐1(XVII) chain, and dystonin showed linear expression along the basal membrane, indicating the presence of type I hemidesmosomes. Plectin stained most epithelial cell membranes and remained unphosphorylated at S4642. In OLP, most hemidesmosomal molecules examined showed disturbed expression consisting of discontinuous increases, apicolateral location, and/or intracellular accumulation. Plectin showed S4642‐phosphorylation at the basement membrane, and deposits of laminin‐α3 and laminin‐γ2 were found within the connective tissue. The disturbed expression of hemidesmosomal proteins in OLP indicates deficient attachment of the basal cell layer, which can contribute to detachment and cell death of basal keratinocytes seen in the disease.

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Section: Discussionmentioning

confidence: 99%

Composition of hemidesmosomes in basal keratinocytes of normal buccal mucosa and oral lichen planus

Schreurs

Balta

Karatsaidis

et al. 2020

European J Oral Sciences

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“…Type 17 collagen coordinates cell proliferation in interfollicular epidermis (23). Its function was shown to be defective in human epidermolysis bullosa (24). It is possible that its overexpression in DSLD horses explains the presence of loose wrinkly skin, patches of grey hair, and bruises in some of these horses (personal communications).…”

Section: Discussionmentioning

confidence: 99%

Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis

Haythorn¹,

Young²,

Stanton³

et al. 2020

Preprint

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Background Equine Degenerative Suspensory Desmitis (DSLD) is a systemic connective tissue disorder first identified in Peruvian Paso horses, but afflicting other horse breeds as well. Inappropriate accumulation of proteoglycans in connective tissues, most prominently in tendons and ligaments leads to progressive and debilitating lameness and pain. It is largely unknown what drives the overproduction of proteoglycans, but our previous studies suggest involvement of bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor β (TGFβ) family, impacting synthesis of proteoglycans. To identify potential players in pathogenesis of DSLD a new approach utilizing next generation sequencing was undertaken. Methods Next generation sequencing was performed using RNA extracted from skin biopsies of six control Peruvian Pasos and six horses with DSLD (4 Peruvian Pasos and 2 Warmbloods). The CuffDiff result sets were validated with algorithms used to run them. This was based on the determined False Discovery Rates derived from the P-values adjusted for multiple testing for any given result. Results Bioinformatics analysis of transcriptomes revealed differential expression of over 1500 genes, including increased expression of genes for several growth factors (most prominently BMP2, FGF5, CTGF, members of the EGF family), of mediators of signaling (Fos, Myc, MAPK system), and keratins. Two genes encoding for enzymes involved in synthesis of hyaluronan were also overexpressed. Gene expression was decreased for protein cores of many proteoglycans, several growth factors, most collagens and many peptides with immune function. Conclusions The overexpression of BMP2 correlates well with our previous data. However, the decrease in expression of numerous proteoglycans was unexpected. A mutation in a gene of a less characterized proteoglycan and/or glycosyltransferase with subsequent increased production of hyaluronan and/or a proteoglycan(s) undetected in our study could account for the systemic proteoglycan deposition. Decreased collagen gene expression indicates abnormal connective tissue metabolism. The increased expression of keratin genes and FGF5 supports reports of skin abnormalities in DSLD. Underexpression of immune function genes corresponds with lack of inflammation in DSLD tissues. Finally, though the proteoglycan and/or glycosaminoglycan abundant in DSLD has not been identified, we validated our previous data, including overexpression of BMP2 , and systemic nature of DSLD due to disturbed metabolism of the extracellular matrix.

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“…6, Supplemental data). Type 17 collagen regulates Wnt pathway and coordinates cell proliferation in interfollicular epidermis [23] and hair follicle stem cells [23,24], and upregulates keratins.…”

Section: Collagens and Other Ecm Componentsmentioning

confidence: 99%

Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis

et al. 2020

View full text Add to dashboard Cite

Background Equine degenerative suspensory ligament desmitis (DSLD) is a systemic connective tissue disorder first identified in Peruvian Paso horses but afflicting other horse breeds as well. Inappropriate accumulation of proteoglycans in connective tissues, most prominently in tendons and ligaments, leads to progressive and debilitating lameness and pain. It is largely unknown what drives the overproduction of proteoglycans, but our previous studies suggest involvement of bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor-β (TGFβ) family, impacting synthesis of proteoglycans. To identify potential players in pathogenesis of DSLD a new approach utilizing next generation sequencing was undertaken. Methods Next generation sequencing was performed using RNA extracted from skin biopsies of six control Peruvian Pasos and six horses with DSLD (4 Peruvian Pasos and 2 warmbloods). The CuffDiff result sets were validated with algorithms used to run them. This was based on the determined false discovery rates derived from the P values adjusted for multiple testing for any given result. Results Bioinformatics analysis of transcriptomes revealed differential expression of over 1500 genes, including increased expression of genes for several growth factors (most prominently BMP2, FGF5, CTGF, many members of the EGF family), and mediators of signaling (Fos, Myc, MAPK system), and keratins. Two genes encoding for enzymes involved in synthesis of hyaluronan were also overexpressed. Gene expression was decreased for protein cores of many proteoglycans, several growth factors, most collagens, and many peptides with immune function. Conclusions The overexpression of BMP2 correlates well with our previous data. However, the decrease in expression of numerous proteoglycans was unexpected. A mutation in a gene of a less characterized proteoglycan and/or glycosyltransferase with subsequent increased production of hyaluronan and/or a proteoglycan(s) undetected in our study could account for the systemic proteoglycan deposition. Decreased collagen gene expression indicates abnormal connective tissue metabolism. The increased expression of keratin genes and FGF5 supports reports of skin abnormalities in DSLD. Underexpression of immune function genes corresponds with lack of inflammation in DSLD tissues. Finally, though the proteoglycan and/or glycosaminoglycan abundant in DSLD has not been identified, we validated our previous data, including overexpression of BMP2, and systemic nature of DSLD due to disturbed metabolism of the extracellular matrix.

show abstract

Life before and beyond blistering: The role of collagen XVII in epidermal physiology

Cited by 51 publications

References 96 publications

Composition of hemidesmosomes in basal keratinocytes of normal buccal mucosa and oral lichen planus

Composition of hemidesmosomes in basal keratinocytes of normal buccal mucosa and oral lichen planus

Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis

Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis

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