Associations between IGFBP1 gene polymorphisms and the risk of preeclampsia and fetal growth restriction

Peng, Xianglan; He, Dong; Peng, Rui; Feng, Jianyang; Chen, Dunjin; Xie, Hong‐Kai; Li, Qixuan; Guo, Yitong; Zhou, Jiaxiong; Chen, Yang; He, Hong

doi:10.1038/s41440-023-01309-8

Cited by 7 publications

(2 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, IGFBP1overexpression inhibited the proliferation, invasion, migration, and apoptosis of HTR-8/SVneo trophoblast cell line ( 43 ). Though elevated decidual and plasm IGFBP1seems to be a protected maker in the early gestation on the perspective of decidualization ( 44 ), at the third trimester, over-expression of IGFBP1 might be a symptom of dysfunctional trophoblast. Thus, the SPP1+IGFBP1+ EVT2 cells might contribute to inflammatory fibrosis in the PE placenta and may play an important role in the pathogenesis of PE.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in this gene can increase a tumor’s responsiveness to immune checkpoint inhibitors and improve the efficacy of targeted drug therapy ( 47 ), but again, there is a lack of basic research on the relationship between this gene and the pathogenesis of PE. Another obvious change in EVTs from the PE group compared to control cells was the downregulation of IGF2 ( 41 – 44 ). IGF2 and its lncRNA IGF2-AS -encoded peptide are important for trophoblast proliferation ( 48 , 49 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Single-cell profiling reveals immune disturbances landscape and HLA-F-mediated immune tolerance at the maternal-fetal interface in preeclampsia

Luo,

Liu,

Guo

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

BackgroundPreeclampsia is a pregnancy-specific disorder that always causes maternal and fetal serious adverse outcome. Disturbances in maternal immune tolerance to embryo at the maternal-fetal interface (MFI) may be associated with preeclampsia onset. Recent studies have revealed the reduced expression pattern of HLA-F at the MFI in preeclampsia, while the mechanism of it mediating maternal fetal immune tolerance has not been revealed.MethodsSingle-cell RNA sequencing on placental decidua was performed to reveal the immune disturbances landscape at the MFI in preeclampsia. Human Jar cells and NK-92MI cells were employed to study the role of HLA-F in trophoblasts and lymphocyte.ResultsA total of 101,250 cells were classified into 22 cell clusters. Disease-related IGFBP1+SPP1+ extracellular villus trophoblast (EVT) was identified in the preeclamptic placental decidua, accompanied by newly discovered immune cellular dysfunction such as reduced ribosomal functions of NK populations and abnormal expression of antigen-presenting molecules in most cell clusters. Certain genes that are characteristic of the intermediate stage of myeloid or EVT cell differentiation were found to have unexplored but important functions in the pathogenesis of preeclampsia; specifically, we detected enhanced cell cross-talk between IGFBP1+SPP1+ EVT2 or SPP1+M1 cells and their receptor cell populations at the MFI of PE patients compared to controls. With respect to HLA-F, mIF staining confirmed its reduced expression in PE samples compared to controls. Over-expression of HLA-F in Jar cells promoted cell proliferation, invasion, and migration while under-expression had the opposite effect. In NK-92MI cells, over-expression of HLA-F increased the secretion of immunoregulation cytokines such as CSF1 and CCL22, and promoted adaptive NKG2C+NK cell transformation.ConclusionsWe revealed the immune disturbance landscape at the MFI in preeclampsia. Our findings regarding cellular heterogeneity and immune cellular dysfunction, as revealed by scRNA-seq, and the function of HLA-F in cells provide new perspectives for further investigation of their roles in the pathogenesis of preeclampsia, and then provide potential new therapeutic target.

show abstract

Section: Discussionmentioning

confidence: 99%