Activation of latent transforming growth factor‐β1 is induced by mannose 6‐phosphate/insulin‐like growth factor‐II receptor
Notice bibliographique
Résumé
This study was conducted to further explore the mechanism of transforming growth factor beta1 (TGF-beta1) activation, which plays a critical role in many physiological and pathological conditions. We have previously shown that the large (270 kDa), but not small (40 kDa), mannose 6-phosphate receptors facilitate the cellular response to latent TGF-beta1 released from genetically modified cells. In this study, we explored the role of cell membrane associated transglutaminase and plasmin in mannose 6-phosphate receptor induced latent TGF-beta activation using MS and MS-9 cells bearing either no receptors or the 270 kDa mannose 6-phosphate/insulin-like growth factor II receptors, respectively. As a source of latent TGF-beta1, PA317 cells were transfected with either pLin-TGF-beta1 vector or pLin retroviral vector with no TGF-beta1 insert using calcium phosphate precipitation. The latency and bioactivity of TGF-beta1 in conditioned medium derived from transfected PA317 cells were evaluated by enzyme-linked immunosorbent assay and mink lung epithelial cell growth inhibition assay, respectively. The level of latent TGF-beta1 was 13-fold higher (20.1 +/- 0.4 vs. 1.5 +/- 0.03 ng/ml) in conditioned medium from pLin-TGF-beta1 transfected cells than that of control. The latency and bioactivity of TGF-beta1 released from pLin-TGF-beta1 transfected cells were confirmed by evaluation of 3H-thymidine incorporation in Mv1Lu epithelial cells treated with non- and heat-activated 10% conditioned medium. The results showed a significantly lower 3H-thymidine incorporation in Mv1Lu epithelial cells treated with heat-activated PA317 conditioned medium (4% of control) relative to those treated with either control or nonheated conditioned medium. This inhibition was abrogated by addition of 40 microg/ml of TGF-beta1 neutralizing antibody. The level of 3H-thymidine incorporation was then evaluated in MS-9 cells receiving Dulbecco's modified Eagle medium containing either 0% 10%, 30% or 50% volumes of nonactivated PA317 conditioned medium for 24 hours. The results showed a markedly lower proliferation in response to 30% and 50% conditioned medium used in MS-9 cells. Under similar experimental conditions, addition of only mannose 6-phosphate, but not fructose 6-phosphate or mannose 1-phosphate, at 1 mM concentration restored the MS-9 cell proliferative response to latent TGF-beta1. The inhibitory effects of latent TGF-beta1 on MS-9 cell proliferation were restored by addition of either TGF-beta1 neutralizing antibody or cystamine, a transglutaminase inhibitor. In contrast, addition of aprotinin, a plasmin inhibitor, had a marginal influence on inhibitory effects of latent TGF-beta1 on MS-9 cell proliferation. Interestingly, a mixture of latent TGF-beta1 + MS-9 cell membranes, but not MS cell membranes, also inhibited the mink lung epithelial cell proliferation (34% of control). These findings indicate that mannose 6-phosphate/insulin-like growth factor II receptors are involved in latent TGF-beta activation and that is at least partly dependent on cell membrane associated transglutaminase, but not on plasmin.
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 ».