FOSL1 mediates collagen synthesis and myofibroblast transformation in aortic fibroblasts under Ang II-induced aortic...

Due to the lack of effective drug therapies, aortic dissection is associated with extremely high mortality rates. Previous studies have demonstrated that FOS-like antigen 1 (FOSL1) plays a role in atherosclerosis and tumor progression. However, the mechanism of FOSL1 in AD remains largely unknown. Therefore, in this study, we aimed to clarify the potential mechanism of FOSL1 in AD and provide a theoretical basis for clinical applications. AD is a life-threatening cardiovascular emergency characterized by a tear in the inner layer of the aorta, resulting in separation of the wall layers and associated with high morbidity and mortality. Understanding the molecular mechanisms driving AD is essential for developing targeted therapies. This study explores the role of the transcription factor FOSL1, known for its involvement in stress response, fibrosis, and cellular differentiation, in AD pathogenesis, with specific focus on collagen deposition and fibroblast-to-myofibroblast transition. Understanding the molecular mechanisms underlying AD is critical for developing novel therapeutic strategies. This study aimed to investigate the role of FOSL1, a transcription factor implicated in cellular differentiation, stress response, and fibrosis, in the pathogenesis of AD and its relationship with collagen deposition and fibroblast phenotype transformation. The role of FOSL1 was investigated by analyzing the Gene Expression Omnibus dataset and evaluating in vitro and in vivo models. Immunohistochemistry and Immunofluorescence assays were used to determine the functional localization of FOSL1 in cells. The effect of FOSL1 expression levels on the efficacy of Naringenin in treating AD was analyzed through combined in vivo and in vitro Naringenin experiments. FOSL1 expression was upregulated in AD, and FOSL1 promoted the proliferation of aortic adventitial fibroblasts in vitro and in vivo. FOSL1 overexpression significantly increased collagen-related protein expression and induced fibroblast phenotype transformation. However, Naringenin reduced AD incidence and severity in vitro and in vivo. Notably, a decrease in FOSL1 expression enhanced the therapeutic effect of Naringenin in AD. FOSL1 is a key regulator in adventitial remodeling during AD, contributing to the proliferation and fibroblast phenotype transformation of adventitial fibroblasts. FOSL1 could serve as a potential target to improve the sensitivity of Naringenin-based therapy.