Activation of FXR regulates oxidative stress responses in human keratinocytes.

Psoriasis is a chronic and inflammatory skin disease that is characterized by red plaques covered with silvery-white scales. The pathogenesis of psoriasis involves a complex interplay between keratinocytes and immune cells, featuring of psoriasis include hyperproliferation and aberrant differentiation of keratinocytes in the epidermis, infiltration of immune cells, and angiogenesis in the dermis. Overall design: In this study, we use human epidermal keratinocytes (HaCaT cells) as an in vitro model to examine the relationship between Farnesoid X Receptor (FXR) signaling and cellular lipid metabolism, focusing on bile acid (BA) homeostasis. We hypothesize that the BA-FXR regulatory axis plays a pivotal role in keratinocyte lipid handling and inflammatory responses, contributing to the pathophysiology of psoriatic skin lesions. Through integrated analyses of BA species, FXR activation status, and downstream lipid-metabolic pathways, we aim to elucidate the mechanistic basis by which BA-FXR signaling influences lipid synthesis, storage, catabolism, and BA-mediated inflammatory signaling in HaCaT cells. This study employs quantitative BA profiling, FXR perturbation (agonism/antagonism), lipidomics, and transcriptomic/proteomic readouts to map the regulatory network. By comparing in vitro findings with observations from psoriatic skin samples, we will assess the translational relevance of the BA–FXR axis as a therapeutic target for psoriasis and related inflammatory dermatoses.