Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertrophic scar (HTS) represents the dermal equivalent of fibroproliferative disorders. Fibroblasts from the deep dermis are implicated in the development of HTS after injuries that involve deeper areas of the skin. However, fibroblasts that reside in the superficial layer of the skin show antifibrotic properties, and injuries limited to this area heal with little or no scarring. Previously, cellular and molecular characteristics of superficial fibroblasts and deep dermal fibroblasts that may influence HTS formation were analyzed. In this study, differences in cellular behavior between superficial fibroblasts and deep dermal fibroblasts that may also affect the development of HTS or tissue fibrosis were further characterized. Immunostaining and migration, adhesion, apoptosis, and cell viability assays were performed in fibroblasts from the superficial and deep dermis. Reverse-transcription polymerase chain reaction was used to examine the gene expression of molecules involved in cell death after treatment of fibroblasts with decorin. When compared with superficial fibroblasts, deep dermal fibroblasts showed lower migration rates. Although all the fibroblasts tested showed no difference in adhesion to fibronectin, superficial fibroblasts demonstrated increased apoptotic and dead cells when treated with decorin. Decorin resulted in a significant increase in the expression of apoptosis markers, histone-1, caspase-1, caspase-8, and p53 in superficial fibroblasts when compared with deep dermal fibroblasts. Taken together, the findings suggest that reduced migration, lack of decorin, and resistance of deep dermal fibroblasts to decorin-induced apoptosis may result in hypercellularity in injuries involving the deep dermis, leading to deposition of excess extracellular matrix and HTS formation.
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PMID:Deep dermal fibroblasts refractory to migration and decorin-induced apoptosis contribute to hypertrophic scarring. 2221 76

The thymus is a lymphoid organ that governs the development of a diverse T-cell repertoire capable of defending against nonself-antigens and avoiding autoimmunity. However, the thymus can also succumb to different diseases. Hypertrophic diseases, such as thymomas, are typically associated with impairment of negative selection, which leads to autoimmune disease, or disruption of positive selection, which results in immunodeficiency. Hypotrophic diseases of the thymus can manifest during acute infections, cancer, allogeneic bone marrow transplantation, or with aging. This condition leads to decreased immune function and can be treated by either replacing lost thymic tissue or by preventing thymic tissue death. Studies have demonstrated the critical role of caspase-8 in regulating apoptosis in the thymus. In this review, we discuss how pharmacological activation and inhibition of caspase-8 can be used to treat hypertrophic and hypotrophic diseases of the thymus, respectively, to improve its function.
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PMID:Pharmacological modulation of caspase-8 in thymus-related medical conditions. 2506 Jun 74