Biomedicines, Год журнала: 2024, Номер 12(12), С. 2723 - 2723

Опубликована: Ноя. 28, 2024

Successful skin wound healing is dependent on an interplay between epidermal keratinocytes and dermal fibroblasts as they react to local extracellular factors (DAMPs, PAMPs, cytokines, etc.) surveyed from that environment by numerous membrane receptors (e.g., TLRs, cytokine receptors, etc.). In turn, those are the start of a cytoplasmic signaling pathway where balance key effective and, needed, cell matrix regeneration. When directed through NF-κB, these routes lead transient responses benefit initiating immune recruitment, replication, chemokine production, protein synthesis. The converse can also occur, ongoing canonical NF-κB activation leads chronic, hyper-responsive states. Here, we assess three players, TAK1, TNFAIP3, TNIP1, in regulation activation, which, because their distinctive yet inter-related functions, either promote or limit activation. Their balanced function integral successful healing, given significant control over expression inflammation-, fibrosis-, remodeling-associated genes. Intriguingly, proteins have been emphasized dysregulated central systemic sclerosis (SSc). Notably, diffuse SSc shares some tissue features similar excessive inflammatory/fibrotic response without eventual resolution. Taking cue certain instances aberrant having shared aspects, e.g., chronic inflammation fibrosis, this review looks for first time, our knowledge, at what pathologies might common regarding progression NF-κB-mediated signaling. Additionally, while TNIP1 often investigated reported individually, propose them here whose consequences very highly interconnected focus NF-κB. We thus highlight emerging promise clinical derived improved understanding signal modulators. Depending protein, its indirect direct pharmacological has reported. Current findings support further intensive studies points both basic healthy cells well with goal targeting translational multiple cutaneous situations, whether stemming acute injury response.

Язык: Английский