Abstract
Intrahepatic cholestasis of pregnancy (ICP) occurs mainly during the third trimester of gestation and is characterized by pruritus and elevated serum bile acid levels. The pathogenesis of this disease has yet to be elucidated. The nonclassical human leukocyte antigen G (HLA-G) is a trophoblast-specific molecule and is involved in the regulation of maternal immune response at the maternal-fetal interface. MicroRNAs (miRNAs) have an important role in a number of physiological and pathological processes. However, the roles of HLA-G and miRNAs in immune response in the pathogenesis of ICP have yet to be elucidated. In the present study, the expression of HLA-G and miR-148a in the placenta of patients with ICP was investigated. The mRNA and protein expression levels of HLA-G were markedly reduced in the placenta of patients with ICP compared with the levels in healthy pregnant females, and were negatively correlated with serum total bile acid (TBA) levels. It was also observed that miR-148a levels were markedly upregulated in the placenta and peripheral blood of patients with ICP. Furthermore, the mRNA and protein expression levels of HLA-G in the placenta were negatively correlated with the miR-148 levels in the placenta, but not in the peripheral blood, while the miR-148a levels in the placenta were positively correlated with serum TBA levels. These results suggest that the downregulation of HLA-G is probably caused by the upregulation of miR-148a in the placenta, and miR-148a in the placenta may contribute to the pathogenesis of ICP via the inhibition of HLA-G expression.
Highlights
Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder specific to pregnancy, characterized by maternal pruritus in the third trimester of gestation and increased levels of serum bile acid
Patients with ICP were verified by determining the levels of serum total bile acid (TBA), alanine transaminase (ALT) and aspartate transaminase (AST; data not shown)
These results indicate Human leukocyte antigen G (HLA‐G) may be involved in the pathogenesis of ICP
Summary
Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder specific to pregnancy, characterized by maternal pruritus in the third trimester of gestation and increased levels of serum bile acid. The symptoms disappear quickly in mothers following delivery, the high level of bile acid is detrimental to the development of fetal organs and the functions of the umbilical cord and placenta, and may result in preterm labor and elevated prenatal mortality [1,2,3]. We demonstrated that the expression of HLA‐G protein was significantly reduced in the extravillous trophoblasts of patients with ICP, whilst tumor necrosis factor‐α (TNF‐α) and TNF‐α/interleukin‐4 (IL‐4) were significantly elevated in patients with ICP [9]. It may be predicted that the downregulation of HLA‐G and the imbalance of T helper 1 (Th1)/Th2 cytokines may be associated with the occurrence of ICP
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