loading...| Preferred Name | Ichthyosis Vulgaris | |
| Synonyms |
PathwayType: signaling PMID: 23301728 Organ: skin NodeType: Pathway PMID: 26945532 Pathway_Author: V. Sobolev ORCID:0000-0003-4779-156X Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-fa25ee7c-2edd-474f-bcd8-dce84a2818b2 Description: Ichthyosis vulgaris is the most common ichthyosis, with an incidence of 1:250 to 1:1000. Pathway is built manually using published studies. Organ_System: integumentary system PMID: 26844893 Notes: Headnote: Ichthyosis is a family of genetic disorders with dry, scaly and thickened skin. Ichthyosis vulgaris (IV) is the most common form of ichthyosis, with an incidence of 1:250 to 1:1000. IV is the mildest form of hereditary non-syndromic ichthyosis, characterized by xerosis, scaling, pruritus and eczema, and is strongly associated with atopic manifestations. IV is considered a single gene disease caused by mutations in the gene encoding profillagrin, which is the precursor for fillagrin (FLG). Signaling description: Profilaggrin is cleaved by several enzymes and converted into functional filaggrin monomer. The profilaggrin linker domain is cleaved by KLK5. Kallikrein-related peptidase 5(KLK5) is a major serine protease found in the skin, secreted from lamellar granules following its expression in the stratum granulosum and activated in the extracellular space of the stratum corneum. Filaggrin monomers, the product of biochemical processing, bind to keratin 1 or keratin 10 and bundle keratin intermediate filaments in the lower stratum corneum. Filaggrin monomers then undergo citrullination mediated by peptidyl arginine deiminase 1 (PADI1) and PADI3. Deiminated filaggrin monomers are cleaved by calpain 1 and caspase-14, yielding free amino acids following degradation by bleomycin hydrolase in the upper stratum corneum. Free aminoacids serve as natural moisturizing factors in human skin. Overall, a significant role of FLG mutations in the pathogenesis of ichthyosis vulgaris has been proven. Outcome effects: Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and the formation of the protective skin barrier. In the outer granular layer of the epidermis, filaggrin is associated with keratin intermediate filaments and it aids their packing into bundles. In terminal differentiation, filaggrin is cross-linked to the cornified cell envelope, which constitutes an insoluble barrier in the stratum corneum to protect the organism against environmental agents and to prevent epidermal water loss. Animal data: Role of Kallikrein-related peptidase 5(KLK5) as the major serine protease found in the skin for profilaggrin was revealed from animal model experiments. Highlighted proteins: Lipids, amino acids and H2O are highlighted in blue in order to illustrate the disruption of protective skin barrier which causes epidermal water loss in the stratum corneum. Mutated proteins: FLG mutated in IV is shown in white-out style. PMID: 23870202 CellType: keratinocyte Source: Diseases |
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urn:agi-pathway:uuid-fa25ee7c-2edd-474f-bcd8-dce84a2818b2 |
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PS:PathwayType PS:Description PS:Pathway_Author PS:Link PS:CellType PS:Organ_System PS:PMID PS:NodeType PS:Notes PS:Organ PS:Source |
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PathwayType: signaling PMID: 23301728 Organ: skin NodeType: Pathway PMID: 26945532 Pathway_Author: V. Sobolev ORCID:0000-0003-4779-156X Description: Ichthyosis vulgaris is the most common ichthyosis, with an incidence of 1:250 to 1:1000. Pathway is built manually using published studies. Organ_System: integumentary system PMID: 26844893 Notes: Headnote: Ichthyosis is a family of genetic disorders with dry, scaly and thickened skin. Ichthyosis vulgaris (IV) is the most common form of ichthyosis, with an incidence of 1:250 to 1:1000. IV is the mildest form of hereditary non-syndromic ichthyosis, characterized by xerosis, scaling, pruritus and eczema, and is strongly associated with atopic manifestations. IV is considered a single gene disease caused by mutations in the gene encoding profillagrin, which is the precursor for fillagrin (FLG). Signaling description: Profilaggrin is cleaved by several enzymes and converted into functional filaggrin monomer. The profilaggrin linker domain is cleaved by KLK5. Kallikrein-related peptidase 5(KLK5) is a major serine protease found in the skin, secreted from lamellar granules following its expression in the stratum granulosum and activated in the extracellular space of the stratum corneum. Filaggrin monomers, the product of biochemical processing, bind to keratin 1 or keratin 10 and bundle keratin intermediate filaments in the lower stratum corneum. Filaggrin monomers then undergo citrullination mediated by peptidyl arginine deiminase 1 (PADI1) and PADI3. Deiminated filaggrin monomers are cleaved by calpain 1 and caspase-14, yielding free amino acids following degradation by bleomycin hydrolase in the upper stratum corneum. Free aminoacids serve as natural moisturizing factors in human skin. Overall, a significant role of FLG mutations in the pathogenesis of ichthyosis vulgaris has been proven. Outcome effects: Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and the formation of the protective skin barrier. In the outer granular layer of the epidermis, filaggrin is associated with keratin intermediate filaments and it aids their packing into bundles. In terminal differentiation, filaggrin is cross-linked to the cornified cell envelope, which constitutes an insoluble barrier in the stratum corneum to protect the organism against environmental agents and to prevent epidermal water loss. Animal data: Role of Kallikrein-related peptidase 5(KLK5) as the major serine protease found in the skin for profilaggrin was revealed from animal model experiments. Highlighted proteins: Lipids, amino acids and H2O are highlighted in blue in order to illustrate the disruption of protective skin barrier which causes epidermal water loss in the stratum corneum. Mutated proteins: FLG mutated in IV is shown in white-out style. PMID: 23870202 CellType: keratinocyte Source: Diseases |
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| id |
urn:agi-pathway:uuid-fa25ee7c-2edd-474f-bcd8-dce84a2818b2 |
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| label |
Ichthyosis Vulgaris |
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| notation |
uuid-fa25ee7c-2edd-474f-bcd8-dce84a2818b2 |
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| prefLabel |
Ichthyosis Vulgaris |
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urn:agi-folder:ichthyosis urn:agi-folder:integumentary_system urn:agi-folder:i |
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| subClassOf |
urn:agi-folder:ichthyosis urn:agi-folder:integumentary_system urn:agi-folder:i |