Identification of stage-specific genes associated with lupus nephritis and response to remission induction in NZB/W and NZM2410 mice
Notice bibliographique
Résumé
Lupus nephritis affects 30 to 70% of systemic lupus erythematosus (SLE) patients and its treatment remains insufficiently effective and excessively toxic. Although biomarkers for nephritis are being identified there is still no reliable way of predicting an impending renal flare or determining which patients will respond to therapy. Because human renal tissue cannot be obtained sequentially during remission and relapse, animal models are often used to study progression of lupus nephritis. To elucidate the molecular mechanisms involved in renal inflammation during the progression, remission and relapse of nephritis we performed a transcriptome analysis of renal tissue from two murine lupus models, NZB/WF1 mice that develop proliferative glomerulonephritis and NZM2410 mice that develop glomerulosclerosis with minimal inflammation. Kidneys from NZB/W F1 and NZM2410 mice were harvested at intervals during their disease course or after remission induction with either combination cyclophosphamide/costimulatory blockade or with BAFF inhibition. Genome-wide expression profiles were obtained from microarray analysis of perfused kidneys. Real-time PCR analysis for selected genes was used to validate the microarray data. Comparisons between groups using SAM, and unbiased analysis of the entire dataset using singular value decomposition and self-organizing map were performed. Few changes in the renal molecular profile were detected in pre-nephritic kidneys but a significant shift in gene expression, reflecting inflammatory cell infiltration and complement activation, occurred at proteinuria onset. Subsequent changes in gene expression predominantly affected mitochondrial dysfunction and metabolic stress pathways. Remission induction reversed most, but not all, of the inflammatory changes and progression towards relapse was associated with recurrence of inflammation, mitochondrial dysfunction and metabolic stress signatures. Endothelial cell activation, tissue remodeling and tubular damage were the major pathways associated with loss of renal function. Immune cell infiltration and activation is associated with proteinuria onset and reverses with immunosuppressive therapy but disease progression is associated with renal hypoxia and metabolic stress. Optimal therapy of SLE nephritis may therefore need to target both immune and nonimmune disease mechanisms. In addition, the overlap of a substantial subset of molecular markers with those expressed in human lupus kidneys suggests potential new biomarkers and therapeutic targets.
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 | 0,007 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| 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 ».