Antifibrotic effects of 2-carba cyclic phosphatidic acid (2ccPA) in systemic sclerosis: contribution to the novel treatment.

Background: Cyclic phosphatidic acid (cPA) has an inhibitory effect on the autotaxin (ATX)/lysophosphatidic acid (LPA) axis, which has been implicated to play an important role in the progression of fibrosis in systemic sclerosis (SSc). The purpose of this study is to assess the antifibrotic activity of cPA for the treatment of SSc using SSc skin fibroblasts and an animal model of bleomycin-induced skin fibrosis.

Methods: We used a chemically stable derivative of cPA (2ccPA).

Mouse 3T3-L1 cells acquire resistance against oxidative stress as the adipocytes differentiate via the transcription factor FoxO.

Repression of excessive increase and enlargement of adipocytes that is closely associated with obesity is effective in the prevention and treatment of metabolic syndrome. Generally, apoptosis is induced in cells via a wide variety of intracellular or extracellular substances, and recently, it has been suggested that the FoxO subfamily is involved in the induction of apoptosis. We aimed to elucidate the mechanism of FoxO-mediated apoptosis-induction in the adipocytes under the reactive oxygen species (ROS) stimulus.