ABSTRACT
Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.
Subject(s)
Mice , Animals , Humans , Hepatitis, Autoimmune/pathology , Signal Transduction , Disease Models, Animal , Stem CellsABSTRACT
The ubiquitin-specific protease ( USP) inhibitors influence many crucial cellular activities and some immune processes, such as anti-inflammatory, anti-infection and anti-tumor by silencing the functions of USP.The main USP inhibitors, which potency and specificity are underlined and current methods for detecting and identifying USP inhibitors are discussed of in this review.