Murine Hyaluronidase 2 Deficiency Results in Extracellular Hyaluronan Accumulation and Severe Cardiopulmonary Dysfunction
Notice bibliographique
Résumé
Hyaluronidase (HYAL) 2 is a membrane-anchored protein that is proposed to hydrolyze hyaluronan (HA) to smaller fragments that are internalized for breakdown. Initial studies of a Hyal2 knock-out (KO) mouse revealed a mild phenotype with high serum HA, supporting a role for HYAL2 in HA breakdown. We now describe a severe cardiac phenotype, deemed acute, in 54% of Hyal2 KO mice on an outbred background; Hyal2 KO mice without the severe cardiac phenotype were designated non-acute. Histological studies of the heart revealed that the valves of all Hyal2 KO mice were expanded and the extracellular matrix was disorganized. HA was detected throughout the expanded valves, and electron microscopy confirmed that the accumulating material, presumed to be HA, was extracellular. Both acute and non-acute Hyal2 KO mice also exhibited increased HA in the interstitial extracellular matrix of atrial cardiomyocytes compared with control mice. Consistent with the changes in heart structure, upper ventricular cardiomyocytes in acute Hyal2 KO mice demonstrated significant hypertrophy compared with non-acute KO and control mice. When the lungs were examined, evidence of severe fibrosis was detected in acute Hyal2 KO mice but not in non-acute Hyal2 KO or control mice. Total serum and heart HA levels, as well as size, were increased in acute and non-acute Hyal2 KO mice compared with control mice. These findings indicate that HYAL2 is essential for the breakdown of extracellular HA. In its absence, extracellular HA accumulates and, in some cases, can lead to cardiopulmonary dysfunction. Alterations in HYAL2 function should be considered as a potential contributor to cardiac pathologies in humans. Hyaluronidase (HYAL) 2 is a membrane-anchored protein that is proposed to hydrolyze hyaluronan (HA) to smaller fragments that are internalized for breakdown. Initial studies of a Hyal2 knock-out (KO) mouse revealed a mild phenotype with high serum HA, supporting a role for HYAL2 in HA breakdown. We now describe a severe cardiac phenotype, deemed acute, in 54% of Hyal2 KO mice on an outbred background; Hyal2 KO mice without the severe cardiac phenotype were designated non-acute. Histological studies of the heart revealed that the valves of all Hyal2 KO mice were expanded and the extracellular matrix was disorganized. HA was detected throughout the expanded valves, and electron microscopy confirmed that the accumulating material, presumed to be HA, was extracellular. Both acute and non-acute Hyal2 KO mice also exhibited increased HA in the interstitial extracellular matrix of atrial cardiomyocytes compared with control mice. Consistent with the changes in heart structure, upper ventricular cardiomyocytes in acute Hyal2 KO mice demonstrated significant hypertrophy compared with non-acute KO and control mice. When the lungs were examined, evidence of severe fibrosis was detected in acute Hyal2 KO mice but not in non-acute Hyal2 KO or control mice. Total serum and heart HA levels, as well as size, were increased in acute and non-acute Hyal2 KO mice compared with control mice. These findings indicate that HYAL2 is essential for the breakdown of extracellular HA. In its absence, extracellular HA accumulates and, in some cases, can lead to cardiopulmonary dysfunction. Alterations in HYAL2 function should be considered as a potential contributor to cardiac pathologies in humans.
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 | 0,001 | 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 ».