Fn14 antagonist L524-0366 exerts protective effect on fibroblasts

The expression of TWEAK and Fn14 was increased in early skin lesions of SSc patients. Fn14 expression on human dermal fibroblasts is significantly increased after stimulation with serum from patients with systemic sclerosis. The interplay between TWEAK and Fn14 is pivotal in the fibrotic progression of various autoimmune diseases. These observations implicate the TWEAK/Fn14 signaling pathway may as a critical player in the pathological advancement of systemic sclerosis; however, the precise underlying mechanisms require further clarification. Thus, human dermal fibroblasts were stimulated by serum from systemic sclerosis patients, and with or without the addition of Fn14 antagonists. We then assessed the antifibrotic effects of this antagonist through RNA sequencing, and preliminary exploration of possible molecular mechanisms. Human dermal fibroblasts (HDF) were treated with serum derived from patients diagnosed with systemic sclerosis (SSc). This treatment was conducted either in the presence or absence of the Fn14 antagonist, L524-0366, to evaluate its potential regulatory effects.