Decreased expression of P-glycoprotein in the placenta of women with autoimmune disease
Notice bibliographique
Résumé
Autoimmune diseases (ADs), such as systemic lupus erythematosus (SLE), require multiple medications to ensure maternal-fetal health during pregnancy. These medications are often substrates for placental transporters that could cross over to the fetal compartment. However, the effects of ADs on placental transporters remain poorly understood. This study aimed to investigate the impact of ADs on placental transporters and key inflammatory cytokines. Human preterm and term placentas from AD-affected women (n = 28) and gestational age-matched controls (n = 38) were collected. The placentas were examined for transporter expression via quantitative real-time PCR and immunodetection. Subgroup analysis and untargeted proteomic analysis of samples from patients with SLE were performed. P-glycoprotein (P-gp/ABCB1) and organic anion transporter 4 (OAT4/SLC22A11) mRNA expression were significantly decreased and expression of T helper 17- associated cytokines were increased in preterm and term AD placenta relative to controls. P-gp protein expression was also downregulated in preterm, but not in term AD placenta. Subgroup analysis of SLE also detected downregulation of P-gp and OAT4 at the mRNA level in preterm samples. Proteomic analysis of SLE and control samples indicated global changes in proteins related to processes like inflammation, oxidative stress, angiogenesis, and hemostasis. These findings elucidate that ADs such as SLE are associated with the downregulation of the ABC transporter P-gp in the placenta as well as global changes to the placenta proteome. Dysregulation of cytokines and associated pathways was also observed and postulated to cause changes in placental transporters. Future studies that validate these mechanisms could offer potential strategies to mitigate inflammation-mediated alterations in placental transporters, ultimately improving fetal and neonatal health. SIGNIFICANCE STATEMENT: Autoimmune diseases have significant effects on the placenta, influencing pregnancy outcomes and the effectiveness of prescribed medications. The study revealed that autoimmune diseases induce inflammatory cytokines in the placenta and were associated with a significant downregulation of P-glycoprotein. Additionally, in patients affected by lupus, proteomics uncovered the enrichment of pathways associated with placental damage and dysfunction. This work will help inform care plans for these patients by identifying clinically relevant proteins that are affected by the disease, improving maternal-fetal outcomes.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».