RESUMEN
Hepatic stellate cells (HSCs) play a role in hepatic fibrosis and sphingosine kinase (SphK) is involved in biological processes. As studies on the regulatory mechanisms and functions of SphK in HSCs during liver fibrosis are currently limited, this study aimed to elucidate the regulatory mechanism and connected pathways of SphK upon HSC activation. The expression of SphK1 was higher in HSCs than in hepatocytes, and upregulated in activated primary HSCs. SphK1 was also increased in liver homogenates of carbon tetrachloride-treated or bile duct ligated mice and in transforming growth factor-ß (TGF-ß)-treated LX-2 cells. TGF-ß-mediated SphK1 induction was due to Smad3 signaling in LX-2 cells. SphK1 modulation altered the expression of liver fibrogenesis-related genes. This SphK1-mediated profibrogenic effect was dependent on SphK1/sphingosine-1-phosphate/sphingosine-1-phosphate receptor signaling through ERK. EGCG blocked TGF-ß-induced SphK1 expression and hepatic fibrogenesis by attenuating Smad and MAPK activation. SphK1 induced by TGF-ß facilitates HSC activation and liver fibrogenesis, which is reversed by EGCG. Accordingly, SphK1 and related signal transduction may be utilized to treat liver fibrosis.
RESUMEN
Anti-LGI1 encephalitis is a subgroup of autoimmune encephalitis, characterized by memory impairments, seizures, and behavioral problems. The diagnosis can be made by clinical manifestation with a help of serum autoantibody test. There was lack of imaging studies to evaluate and monitor the disease activity by anatomical and functional information. Here, we report serial F-FDG PET/CT findings in a patient with anti-LGI1 encephalitis. Intense F-FDG uptake was initially noted in bilateral limbic system at active disease status, and then decreased and eventually normalized according to the clinical improvement after treatment. F-FDG PET/CT can be used to evaluate treatment response of encephalitis.