ArticleInternational journal of molecular medicine2020
Pigment epithelium‑derived factor facilitates NLRP3 inflammasome activation through downregulating cytidine monophosphate kinase 2: A potential treatment strategy for missed abortion.
Article in International journal of molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- The Role of PEDF in the Eye, Bone, and Nervous and Immune Systems.Pharmaceutics · 2025Review
- Mitochondrial dysfunction in pregnancy loss: a review.Molecular and cellular biochemistry · 2025Review
- Curcumin inhibits the activity of ubiquitin ligase Smurf2 to promote NLRP3‑dependent pyroptosis in non‑small cell lung cancer cells.International journal of oncology · 2025Article
- Maternal prenatal systemic inflammation indexes predicts premature neonatal respiratory distress syndrome.Scientific reports · 2024Article
- LincRNA-p21/AIF-1/CMPK2/NLRP3 pathway promoted inflammation, autophagy and apoptosis of human tubular epithelial cell induced by urate via exosomes.Scientific reports · 2024Article
- Article
- The role of pyroptosis in the occurrence and development of pregnancy-related diseases.Frontiers in immunology · 2024Review
- Knockdown of DAPK1 inhibits IL-1β-induced inflammation and cartilage degradation in human chondrocytes by modulating the PEDF-mediated NF-κB and NLRP3 inflammasome pathway.Innate immunity · 2024Article
- Functional Variants Associated WithFrontiers in genetics · 2022Article
- Electroacupuncture Inhibits NLRP3 Activation by Regulating CMPK2 After Spinal Cord Injury.Frontiers in immunology · 2022Article
- Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation.Frontiers in immunology · 2021Article
- Metformin Corrects Glucose Metabolism Reprogramming and NLRP3 Inflammasome-Induced Pyroptosis via Inhibiting the TLR4/NF-Oxidative medicine and cellular longevity · 2021Article
- Clinical Efficacy and Safety Study of Mifepristone with Misoprostol Treatment in Patients with Missed Abortion.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Evaluation of diagnosis and prognosis with anti-mullerian hormone level in early missed abortion.American journal of translational research · 2021Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A number of conditions may underlie the occurrence of missed abortion (MA), including inflammation. Pigment epithelium‑derived factor (PEDF) is a novel mediator of the inflammation‑related nucleotide‑binding oligomerization domain‑like receptor protein 3 (NLRP3) inflammasome, which is associated with several human diseases. However, the association between MA and NLRP3 inflammasome, and whether PEDF is reduced in MA, remain unknown. In the present study, the decidua and chorion tissues of patients who had suffered a MA were examined, and a lipopolysaccharide (LPS)‑induced human chorionic trophoblast HTR8/SVneo cell model was established to mimic MA in vitro. The results revealed that cytidine monophosphate kinase 2 (CMPK2) expression and NLRP3 inflammasome activation, downstream pro‑IL‑18 and pro‑IL‑1β expression, and IL‑18 and IL‑1β release, were all significantly increased in MA tissues or LPS‑induced HTR8/SVneo cells. PEDF reversed the increase in CMPK2 expression and activation of the NLRP3 inflammasome axis and, thus, downregulated the production of mitochondrial reactive oxygen species and mitochondrial DNA release, resulting in reduced lactate dehydrogenase release, and a resultant decrease in cell viability. Recovery of CMPK2 expression abolished all the effects of PEDF, indicating that CMPK2 may be an effector downstream of PEDF. PEDF reduced CMPK2 protein levels but did not affect the mRNA levels, and treatment with the proteasomal inhibitor MG132 significantly reversed this reduction in CMPK2 protein levels. Furthermore, a ubiquitination assay of immunoprecipitation demonstrated that CMPK2 was polyubiquitinated in the presence of LPS, PEDF and MG132. These results indicated that the NLRP3 inflammasome is implicated in the pathogenesis of MA, and PEDF may reduce MA through ubiquitin‑dependent proteasomal degradation of CMPK2 to inhibit NLRP3 activation, which may serve as a novel strategy for preventing or reducing the risk of MA.
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