BAFF and APRIL counterregulate susceptibility to inflammation-induced preterm birth
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA837296 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19173400.fastq.gz | Fastqsanger.gz | |||
| SRR19173401.fastq.gz | Fastqsanger.gz | |||
| SRR19173402.fastq.gz | Fastqsanger.gz | |||
| SRR19173403.fastq.gz | Fastqsanger.gz | |||
| SRR19173404.fastq.gz | Fastqsanger.gz |
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Project description:Emerging clinical evidence points to a function for B cell activating factor (BAFF) in pregnancy. However, a direct role for BAFF-axis members including BAFF, the closely related a proliferation-inducing ligand (APRIL), and their respective receptors in pregnancy has not been examined. This study demonstrates that loss of BAFF results in decreased inflammatory responsiveness and decreased susceptibility to inflammation-induced preterm birth (PTB). In contrast, loss of APRIL increases inflammatory responsiveness and susceptibility to PTB. Consistent with overlapping receptor utilization by BAFF and APRIL, deletion of BAFF-axis receptors is not sufficient to modify susceptibility to PTB. Critically, therapeutic administration of BAFF/APRIL monoclonal antibodies or recombinant proteins is sufficient to manipulate susceptibility to inflammation-induced PTB. Further, macrophages are identified as the principle BAFF producing immune cells at the maternal-fetal interface and BAFF and APRIL divergently manipulate macrophage gene expression and inflammatory function. Genes linked to labor initiation are upregulated in WT and APRIL deficient macrophages while downregulated in BAFF deficient macrophages and correlate with myeloid gene expression in human placental samples during labor. Thus, BAFF and APRIL play important, but divergent, counterregulatory inflammatory roles in pregnancy and provide new therapeutic targets for mitigating the risk of PTB.
2023-08-03 | GSE202811 | GEO
Project description:Preterm birth, defined as birth <37 weeks of gestation, is a leading cause of infant morbidity and mortality. In the United States, approximately 12% of all births are preterm.1 Despite decades of research, there has been little progress in developing effective interventions to prevent preterm birth. In fact, the rate of preterm birth has increased slightly over the last several decades.2 The ultimate goal of the Genomic and Proteomic Network for Preterm Birth Research (GPN-PBR) is to identify possible biomarkers that could predict the susceptibility to spontaneous preterm birth (SPTB) as well as to shed light on the molecular mechanisms involved in its etiologies. Understanding those mechanisms will help us predict SPTB and may facilitate the introduction of more effective prevention and treatment strategies.
2014-08-28 | PXD001268 | Pride
Project description:Purpose: To define the role of the BAFF/APRIL axis in the regulation of adipose tissue homeostasis through RNAseq. Methods: Primary adipocytes were derived from pre-adipocyte precursors of inguinal white adipose from male C57BL/6 mice aged 6-8 weeks. Adipocytes were treated with rBAFF, rAPRIL, or multiple controls for 24 hours. mRNA profiles were generated for each condition, run in biological duplicates, using Illumina HiSeq2000 with single-end, 50bp reads. Differential gene lists were generated by comparing BAFF and APRIL to controls using unpaired ttests. Results:Following mapping an average of 30million reads across 10 samples to the mm10 mouse genome with annotations from UCSC, differential analysis identified genes involved in adipocyte pathways associated with lipid metabolism, lipolysis, and inflammation. Conclusion: BAFF and APRIL modulate modulate white adipocyte lipid handling.
2021-02-08 | GSE131298 | GEO
Project description:Diabetic kidney disease (DKD) is the leading cause of progressive chronic kidney disease in adults in the United States. However, the impact of preterm birth on the progression of DKD has not been studied. The goal of this project is to determine the effect of preterm birth on kidney health in a diabetic mouse model. CD-1 pups born preterm (19 days post conception (dpc)) and term (20 dpc) were studied, and outcomes of the male mice were reported, all compared to term mice. Preterm and term mice were treated with streptozotocin at six weeks to induce hyperglycemia. Body weight and blood sugar were monitored. Histologic, molecular, and imaging techniques were used to characterize the mice at 18 weeks. The preterm mice with diabetes had a lower podocyte density, lower proximal tubular fraction, and more atubular glomeruli compared to the term mice without diabetes. They also had a lower podocyte density and lower renin expression compared to term mice with diabetes. Based on single-cell RNA sequencing, preterm mice with diabetes had increased expression of genes related to the angiogenesis migration pathway-related in endothelial cells and increased expression of genes in the actin adhesion pathway in podocytes compared to term mice with diabetes. Furthermore, the preterm mice with diabetes exhibited a weaker endothelial cell-podocyte interaction compared to term mice with diabetes. These data suggest that preterm birth increases susceptibility to glomerular and tubular damage after a brief “second hit” of hyperglycemia. In conclusion, preterm birth disrupts endothelial-podocyte crosstalk and increases susceptibility to kidney injury induced by hyperglycemia.
2025-06-04 | GSE280780 | GEO
Project description:Diabetic kidney disease (DKD) is the leading cause of progressive chronic kidney disease in adults in the United States. However, the impact of preterm birth on the progression of DKD has not been studied. The goal of this project is to determine the effect of preterm birth on kidney health in a diabetic mouse model. CD-1 pups born preterm (19 days post conception (dpc)) and term (20 dpc) were studied, and outcomes of the male mice were reported, all compared to term mice. Preterm and term mice were treated with streptozotocin at six weeks to induce hyperglycemia. Body weight and blood sugar were monitored. Histologic, molecular, and imaging techniques were used to characterize the mice at 18 weeks. The preterm mice with diabetes had a lower podocyte density, lower proximal tubular fraction, and more atubular glomeruli compared to the term mice without diabetes. They also had a lower podocyte density and lower renin expression compared to term mice with diabetes. Based on single-cell RNA sequencing, preterm mice with diabetes had increased expression of genes related to the angiogenesis migration pathway-related in endothelial cells and increased expression of genes in the actin adhesion pathway in podocytes compared to term mice with diabetes. Furthermore, the preterm mice with diabetes exhibited a weaker endothelial cell-podocyte interaction compared to term mice with diabetes. These data suggest that preterm birth increases susceptibility to glomerular and tubular damage after a brief “second hit” of hyperglycemia. In conclusion, preterm birth disrupts endothelial-podocyte crosstalk and increases susceptibility to kidney injury induced by hyperglycemia.
2025-06-04 | GSE280781 | GEO
Project description:Clinical evidence points to a function for B cell-activating factor (BAFF) in pregnancy. However, direct roles for BAFF-axis members in pregnancy have not been examined. Here, via utility of genetically modified mice, we report that BAFF promotes inflammatory responsiveness and increases susceptibility to inflammation-induced preterm birth (PTB). In contrast, we show that the closely related A proliferation-inducing ligand (APRIL) decreases inflammatory responsiveness and susceptibility to PTB. Known BAFF-axis receptors serve a redundant function in signaling BAFF/APRIL presence in pregnancy. Treatment with anti-BAFF/APRIL monoclonal antibodies or BAFF/APRIL recombinant proteins is sufficient to manipulate susceptibility to PTB. Notably, macrophages at the maternal-fetal interface produce BAFF, while BAFF and APRIL presence divergently shape macrophage gene expression and inflammatory function. Overall, our findings demonstrate that BAFF and APRIL play divergent inflammatory roles in pregnancy and provide therapeutic targets for mitigating risk of inflammation-induced PTB.
| S-EPMC10551044 | biostudies-literature
Project description:Preterm birth is the major cause of newborn and infant mortality affecting nearly one in every ten live births. This study was designed to develop an epigenetic biomarker for susceptibility of preterm birth using buccal cells from the mother, father, and child (triads). MeDIP-seq was used to identify differential DNA methylation regions (DMRs) using a comparison of control term birth versus preterm birth triads. Epigenetic DMR associations with preterm birth were identified for both the mother and father that were distinct and suggest potential epigenetic contributions from both parents. The mother (165 DMRs) and female child (136 DMRs) at p<1e-04 had the highest number of DMRs and were highly similar suggesting potential epigenetic inheritance of the epimutations. The male child had negligible DMR associations. The DMR associated genes for each group involve previously identified preterm birth associated genes.
2022-03-09 | GSE194227 | GEO
Project description:In this study, the molecular signature of placenta membrane from preterm birth placenta was assessed and compared to full-term placenta by proteomic profiling with the aim to identify molecules relevant to preterm birth.
2020-04-17 | MSV000085301 | MassIVE
Project description:Preterm birth is the leading cause of infant mortality resulting in over one million neonatal deaths annually. Maternal urinary tract infection (UTI) during pregnancy increases risk for preterm birth; however, biological processes mediating UTI-associated preterm birth are not well-described. We established a murine maternal UTI model in which challenge with uropathogenic E. coli resulted in preterm birth in about half of dams. Dams experiencing preterm birth displayed excessive bladder inflammation and altered uteroplacental T cell polarization compared to non-laboring infected dams, with no differences in bacterial burdens. Additional factors associated with preterm birth included higher proportions of male fetuses and lower maternal serum IL-10. Furthermore, exogenous maternal IL-10 treatment absolved UTI-associated preterm birth but contributed to fetal growth restriction in this model.
2025-10-23 | GSE280297 | GEO
Project description:Biochemistry of spontaneous preterm birth
| PRJNA493125 | ENA