NF-кB c-Rel modulates pre-fibrotic changes in human fibroblasts.

Skin fibrosis is one central hallmark of the heterogeneous autoimmune disease systemic sclerosis. So far, there are hardly any standardized and effective treatment options. Pathogenic mechanisms underlying fibrosis comprise excessive and uncontrolled myofibroblast differentiation, increased extracellular matrix protein (ECM) synthesis and an intensification of the forces exerted by the cytoskeleton.

Transient epidermal barrier deficiency and lowered allergic threshold in filaggrin-hornerin (FlgHrnr ) double-deficient mice.

Background: Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss-of-function mutations of these genes constitute a risk factor for atopic dermatitis and eczema-related asthma.

c-Rel is a cell cycle modulator in human melanoma cells.

Melanoma progression and resistance to therapy are associated with faulty regulation of signalling molecules including the central transcription factor NF-κB. Increased expression of the c-Rel subunit of NF-κB has been described in progressing melanoma, though mechanistic implications of this upregulation remain unclear. To elucidate the functional role of c-Rel in melanoma biology, we have assessed its expression in human melanoma as well as in melanoma cell lines.

c-Rel in Epidermal Homeostasis: A Spotlight on c-Rel in Cell Cycle Regulation.

To maintain proper skin barrier function, epidermal homeostasis requires a subtly governed balance of proliferating and differentiating keratinocytes. While differentiation takes place in the suprabasal layers, proliferation, including mitosis, is usually restricted to the basal layer. Only recently identified as an important regulator of epidermal homeostasis, c-Rel, an NF-κB transcription factor subunit, affects the viability and proliferation of epidermal keratinocytes.

The c-Rel subunit of NF-κB is a crucial regulator of phenotype and motility of HaCaT keratinocytes.

The transcription factor NF-κB exerts key functions in epidermal homeostasis and carcinogenesis. Its c-Rel subunit is expressed in squamous cell carcinoma, and c-Rel down-regulation results in increased apoptosis, G2/M cell cycle delay with reduced proliferation and aberrant mitotic spindle formation. To further study the impact of c-Rel on essential keratinocyte features such as migration and epithelial morphology, c-Rel was down-regulated in HaCaT keratinocytes by a siRNA approach.

c-Rel downregulation affects cell cycle progression of human keratinocytes.

The c-Rel protein, a member of the NF-κB transcription factor family, exerts unique and distinctive functions in various cell types. Although c-Rel is expressed in human epidermis, its functions in keratinocytes are poorly understood. Our small interfering RNA-based approach of c-Rel silencing in HaCaT keratinocytes induced altered cell morphology toward a spindle-shaped appearance.

The two stem cell microRNA gene clusters C19MC and miR-371-3 are activated by specific chromosomal rearrangements in a subgroup of thyroid adenomas.

Thyroid adenomas are common benign human tumors with a high prevalence of about 5% of the adult population even in iodine sufficient areas. Rearrangements of chromosomal band 19q13.4 represent a frequent clonal cytogenetic deviation in these tumors making them the most frequent non-random chromosomal translocations in human epithelial tumors at all.