Neuromyelitis optica (NMO) is an inflammatory demyelinating disease with generally poor prognosis that selectively targets optic nerves and spinal cord. Although diagnostic criteria for NMO are available, there is still a need for biomarkers, predicting disease development and progression to improve individually tailored treatment. CSF proteins were separated by two-dimensional electrophoresis and identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The interaction between these proteins was further analyzed by Pathway Studio software. Seven protein spots in CSF were significantly altered in NMO patients compared with controls. Identification made by mass spectrometry revealed that the most significant protein was haptoglobin, which was increased in the NMO gels. The subsequent ELISA test were performed to validate it, which confirmed the results of proteomic analysis. Protein network was built, which showed some biological interactions among the seven proteins. These results support a correlation between the level of haptoglobin and NMO. Haptoglobin may be a potential useful biomarker for diagnosis or a medicine target for treatment of NMO.
Context
Dysregulated immune hemostasis occurs in unexplained recurrent spontaneous abortion (URSA). Synthesized by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), hydrogen sulfide (H2S) promotes regulatory T-cell differentiation and regulates immune hemostasis; yet, its role in URSA is elusive.
Objective
To determine if H2S plays a role in early pregnancy and if dysregulated H2S signaling results in RSA.
Design
First-trimester placenta villi and decidua were collected from normal and URSA pregnancies. Protein expression were examined by immunohistochemistry and immunoblotting. Human trophoblast HTR8/SVneo and JEG3 cells were treated with H2S donors; HTR8/SVneo cells were transfected with CBS RNAi or cDNA. Cell migration and invasion were determined by trans-well assays; trophoblast transcriptomes were determined by RNA-seq. Wild-type, CBS-deficient, and CBA/J × DBA/2 mice were treated with CBS and CSE inhibitors or H2S donors to determine the role of H2S in early pregnancy in vivo.
Results
CBS and CSE proteins showed cell-specific expressions but only CBS decreased in the villous cytotrophoblast in URSA vs. normal subjects. H2S donors promoted migration and invasion and MMP-2 and VEGF expression in HTR8/SVneo and JEG3 cells, similar to forced CBS expression in HTR8/SVneo cells. The CBS-responsive transcriptomes in HTR8/SVneo cells contained differentially regulated genes, i.e., IL-1R and PGTS2, that are associated with nuclear factor-κB-mediated inflammatory response. In vivo, dysregulated CBS/H2S signaling significantly increased embryonic resorption and decidual Th1/Th2 imbalance in mice, which was partially rescued by H2S donors.
Conclusion
CBS/H2S signaling maintains early pregnancy possibly via regulating maternal-fetal interface immune hemostasis, offering opportunities for H2S-based immunotherapies for URSA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.