Keratohyalin granules are heterogeneous in ridged and non-ridged human skin: evidence from anti-filaggrin immunogold labelling of normal skin and skin of autosomal dominant ichthyosis vulgaris patients

Günzel, Susanne; Weidenthaler, B; Haußer, Ingrid; Anton‐Lamprecht, I.

doi:10.1007/bf00371777

Cited by 18 publications

(12 citation statements)

References 41 publications

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“…When KHG were present, ultrastructural abnormalities were not detected. The differences between these observations and those reported previously (21,22,34,35), in which ‘crumbly’ KHG were observed, appear to reflect differences in technique. This is supported by the demonstration of a small amount of immunoreactive profilaggrin in the epidermis of an individual with IV and no KHG by immunoelectron microscopy (36).…”

Section: Discussioncontrasting

confidence: 89%

Absence of the granular layer and keratohyalin define a morphologically distinct subset of individuals with ichthyosis vulgaris

Fleckman

Brumbaugh

2002

Experimental Dermatology

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The clinical diagnosis of ichthyosis vulgaris (IV) can be difficult. Abnormalities in the granular layer and the ultrastructure of keratohyalin granules (KHG) suggest that morphology may be helpful. To clarify morphologic findings in IV, 41 clinically affected individuals and 21 unaffected family members or age- and sex-matched controls were studied by light microscopy. In these, the granular layer was totally absent in approximately 50% of affected individuals, while present in all controls. Forty-seven individuals in the light microscopy group were also studied by electron microscopy. Keratohyalin granules were absent in all affected individuals lacking the granular layer by light microscopy. Clinical severity usually correlated with the lack of a granular layer and KHG. Absence of the granular layer was consistent in different anatomic sites and in serial biopsies taken over a 1-3-year period. In a subset of clinically affected, unrelated subjects with moderate to severe involvement, four out of 11 (36%) had similar findings. Keratinocytes cultured from affected individuals with no KHG expressed virtually no detectable profilaggrin protein in vitro. The data suggest that a subset of individuals with moderate to severe IV have a consistently absent granular layer and KHG. Absence of the granular layer and lack of KHG correlated almost perfectly; thus light microscopy offers a convenient means of identifying this subtype of IV. However, both morphologic types of IV were observed within single families. Therefore, the relationship between granular layer abnormalities and IV is complex and requires the study of more affected families. One interpretation of the data is that IV is a multigenic disorder in which one of the genes alters profilaggrin expression. We propose this clinical and histologic phenotype as useful for identifying the gene(s) involved and also for determining whether it represents a modifier or a major locus of the disorder.

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Section: Discussioncontrasting

confidence: 89%

Absence of the granular layer and keratohyalin define a morphologically distinct subset of individuals with ichthyosis vulgaris

Fleckman

Brumbaugh

2002

Experimental Dermatology

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“…Interestingly, some reports previously suggested that keratohyalin granules are heterogeneous and bicomponent in human skin. In fact, keratohyalin consists of a major electron-dense component containing filaggrin and a less electron-dense minor component without filaggrin (Günzel et al 1991; Kastl and Anton-Lamprecht 1990). Although we were not able to analyze keratohyalin granules in our samples, we may hypothesize that keratohyalin may be heterogeneous in normal human skin, especially in ridged skin, as suggested.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the human ridged and non-ridged skin: a comprehensive histological, histochemical and immunohistochemical analysis

Vela-Romera

Carriel

Martín-Piedra

et al. 2018

Histochem Cell Biol

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The structure of the human skin is directly dependent on its location and the mechanical forces to which it is subjected. In the present work, we have performed a comprehensive analysis of the human ridged and non-ridged skin to identify the differences and similarities between both skin types. For this purpose, human skin samples were obtained from dorsal hand skin (DHS), palmar hand skin (PHS), dorsal foot skin (DFS) and plantar foot skin (PFS) from the same cadaveric donors. Histological, histochemical and semiquantitative and quantitative immunohistochemical analyses were carried out to evaluate the epidermis, dermis and basement membrane. Results show that the epithelial layer of ridged skin had larger cell number and size than non-ridged skin for most strata. Melanocytes and Langerhans cells were more abundant in non-ridged skin, whereas Merkel cells were preferentially found in ridged skin. The expression pattern of CK5/6 was slightly differed between non-ridged and ridged skin. Involucrin expression was slightly more intense in non-ridged skin than in ridged skin. Collagen was more abundant in foot skin dermis than in hand skin, and in ridged skin as compared to non-ridged skin. Elastic fibers were more abundant in DHS. Biglycan was more abundant in foot skin than in hand skin. No differences were found for blood and lymphatic vessels. The basement membrane laminin was preferentially found in foot skin. These results revealed important differences at the epithelial, dermal and basement membrane levels that could contribute to a better knowledge of the human skin histology.

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“…Filaggrin deficiency is well known in ichthyosis vulgaris (Gunzel et al, 1991). Defective interaction between keratin and filaggrin is also seen in epidermolytic hyperkeratosis.…”

Section: Discussionmentioning

confidence: 99%

Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation

Egberts

Heinrich

Jensen

et al. 2004

Journal of Cell Science

116

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We previously demonstrated that the aspartate protease cathepsin D is activated by ceramide derived from acid sphingomyelinase. Increased expression of cathepsin D in the skin has been reported in wound healing, psoriasis and skin tumors. We explored specific functions of cathepsin D during epidermal differentiation. Protein expression and enzymatic activity of cathepsin D increased in differentiated keratinocytes in both stratified organotypic cultures and in mouse skin during epidermal barrier repair. Treatment of cultured keratinocytes with exogenous cathepsin D increased the activity of transglutaminase 1, known to cross-link the cornified envelope proteins involucrin and loricrin during epidermal differentiation. Inhibition of cathepsin D by pepstatin A suppressed the activity of transglutaminase 1. Cathepsin D-deficient mice revealed reduced transglutaminase 1 activity and reduced protein levels of the cornified envelope proteins involucrin and loricrin. Also, amount and distribution of cornified envelope proteins involucrin, loricrin, filaggrin, and of the keratins K1 and K5 were significantly altered in cathepsin D-deficient mice. Stratum corneum morphology in cathepsin D-deficient mice was impaired, with increased numbers of corneocyte layers and faint staining of the cornified envelope only, which is similar to the human skin disease lamellar ichthyosis. Our findings suggest a functional link between cathepsin D activation, transglutaminase 1 activity and protein expression of cornified envelope proteins during epidermal differentiation.

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Keratohyalin granules are heterogeneous in ridged and non-ridged human skin: evidence from anti-filaggrin immunogold labelling of normal skin and skin of autosomal dominant ichthyosis vulgaris patients

Cited by 18 publications

References 41 publications

Absence of the granular layer and keratohyalin define a morphologically distinct subset of individuals with ichthyosis vulgaris

Absence of the granular layer and keratohyalin define a morphologically distinct subset of individuals with ichthyosis vulgaris

Characterization of the human ridged and non-ridged skin: a comprehensive histological, histochemical and immunohistochemical analysis

Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation

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