Dysfunctional Keratinocytes Increase Dermal Inflammation in Systemic Sclerosis: Results From Studies Using Tissue‐Engineered Scleroderma Epidermis
نویسندگان
چکیده
Objective Evidence suggests that keratinocyte–fibroblast interactions are abnormal in systemic sclerosis (SSc). The present study was undertaken to investigate potential epidermal dysfunction SSc and its effects on dermal homeostasis. Methods Epidermal equivalents (EEs) were generated using keratinocytes from 6 healthy donors 4 individuals with SSc. Skin EE expression of markers proliferation, differentiation, activation evaluated by immunohistochemistry. transcriptomic profile EEs donor identified RNA sequencing. conditioned medium (CM) used stimulate fibroblasts, their production interleukin-6 (IL-6), IL-8, matrix metalloproteinase 1 (MMP-1), type I collagen, fibronectin assessed enzyme-linked immunosorbent assay. Results Compared EEs, exhibited aberrant enhanced markers, a lower rate basal keratinocyte mitosis, reproducing most the abnormalities observed epidermis. sequencing analysis revealed that, compared characterized homeobox gene family members metabolic oxidative stress molecular pathways. CM fibroblast IL-6, MMP-1, (P < 0.05). Except for collagen fibronectin, this effect 2-fold higher presence form EEs. IL-1 responsible, at least part, keratinocyte-dependent activation. Conclusion recapitulate vivo characteristics epidermis, demonstrating have an intrinsically altered differentiation program, possibly due dysregulation genes family. increased associated epidermis may contribute chronic inflammation fibrosis dermis.
منابع مشابه
Systemic Sclerosis (Scleroderma)
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متن کاملSystemic Sclerosis (Scleroderma)
Systemic sclerosis (SSc) is a multisystem autoimmune disease in which there is increased fibroblast activity resulting in abnormal growth of connective tissue. This causes vascular damage and fibrosis. Fibrosis occurs in skin, the gastrointestinal (GI) tract, heart, lungs and other internal organs. Vascular manifestations include secondary Raynaud's phenomenon, ischaemia of extremities, pulmona...
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ژورنال
عنوان ژورنال: Arthritis & rheumatology
سال: 2021
ISSN: ['2326-5191', '2326-5205']
DOI: https://doi.org/10.1002/art.41659