Inhibition of TMUB1 blocks apoptosis and NF‐κB pathway‐mediated inflammation in recurrent spontaneous abortion
Open Access
- 26 May 2023
- journal article
- research article
- Published by Wiley in Immunity, Inflammation and Disease
- Vol. 11 (5)
- https://doi.org/10.1002/iid3.879
Abstract
Introduction: Approximately 50% of cases with recurrent spontaneous abortion (RSA) have unexplained etiology. Aberrant expression of transmembrane and ubiquitin-like domain containing 1 (TMUB1) is closely related to a series of diseases, including RSA. However, the function and underlying mechanism of TMUB1 in the occurrence of RSA has not been described. Methods: TMUB1 expression was detected in the placental villous tissues of 30 women with normal miscarriages and 12 women with RSA. The pregnant mice were injected intraperitoneally with lipopolysaccharide (LPS) to induce abortion. Human chorionic trophoblast cells were treated with LPS. Pathological analysis of placental tissues was performed by hematoxylin and eosin staining. Results: TMUB1 was highly expressed in the placental villous tissues of RSA patients compared to the patients who underwent induced abortions. After LPS administration, the mice exhibited high embryo absorption and pathological alterations, as well as presented an increase in inflammation and apoptosis (the etiology of RSA induction) in placental tissues. Moreover, the upregulated expression of TMUB1 was also found in placental tissues of LPS-induced mice, and further investigation showed that TMUB1 deficiency blocked embryo loss as well as inhibited apoptotic rate and inflammation after LPS activation. Furthermore, we found that the loss of TMUB1 suppressed the phosphorylation of IkappaB kinase (IKK) alpha/beta and attenuated cytoplasmic-nuclear translocation of nuclear factor-kappa B (NF-kappa B) p65 in LPS-induced cells. Conclusion: Our results indicate that TMUB1 may involve in the modulation of apoptosis and NF-kappa B pathway-mediated inflammation in RSA. Therefore, TMUB1 may develop as a potential biomarker for RSA treatment.Keywords
This publication has 42 references indexed in Scilit:
- Increased placental expression and maternal serum levels of apoptosis-inducing TRAIL in recurrent miscarriagePlacenta, 2013
- Depletion of Invariant NKT Cells Reduces Inflammation-Induced Preterm Delivery in MiceThe Journal of Immunology, 2012
- IL-6 induction of hepatocyte proliferation through the Tmub1-regulated gene pathwayInternational Journal of Molecular Medicine, 2012
- Recurrent pregnancy loss: A disease of inflammation and coagulationJournal of Obstetrics and Gynaecology Research, 2009
- Angiotensin II Activates IκB Kinase Phosphorylation of RelA at Ser536 to Promote Myofibroblast Survival and Liver FibrosisGastroenterology, 2009
- Recurrent miscarriageThe Lancet, 2006
- Circuitry of nuclear factor κB signalingImmunological Reviews, 2006
- HOPS: a novel cAMP-dependent shuttling protein involved in protein synthesis regulationJournal of Cell Science, 2005
- Phosphorylation of NF-κB and IκB proteins: implications in cancer and inflammationTrends in Biochemical Sciences, 2005
- Incidence of Early Loss of PregnancyThe New England Journal of Medicine, 1988