MK5 and ERK3 play overlapping but distinct roles in regulating cardiac fibroblast function
Notice bibliographique
Résumé
Background and objectives Immunoreactivity for MAP kinase‐activated protein kinase‐5 (MK5), a protein serine/threonine kinase, is detected in cardiac ventricular fibroblasts but not myocytes. p38 and ERK3/4 MAP kinases are activators of MK5. However, the regulation of MK5 remains controversial and its physiological functions are poorly understood. Following hemodynamic overload, the increase in collagen mRNA was attenuated in ERK3 and MK5 haploinsufficient mice. In addition, following myocardial infarction, scar size and collagen content were reduced in MK5 +/− mice, compared with MK5 +/+ mice. In addition, MK5 −/− fibroblasts show reduced motility and proliferation. Thus, MK5 may play a role in fibroblast function. The present study was to examine the role of ERK3, a putative activator of MK5, in cardiac fibroblast function. Methods Cardiac ventricular fibroblasts were isolated from MK5 +/+ mice and male Sprague‐Dawley rats. Subconfluent cultures of fibroblasts from passages 2 and 3 were used. Ventricular myocytes were prepared from adult MK5 +/+ mice. Protein expression was determined by immunoblotting. The presence of ERK3‐MK5 complexes was determined by proximity ligation assay (PLA) and co‐immunoprecipitation assays. Cell motility and myofibroblast contraction were studied by scratch‐wound and collagen gel contraction assays, respectively. Results siRNA‐mediated knockdown of MK5 (MK5‐kd) resulted in reduced contraction of collagen gels, reduced cell spreading, and formation of fewer dendritic extensions compared to fibroblasts transfected with scrambled RNA. ERK3 immunoreactivity was detected in fibroblasts but negligible in cardiomyocytes. MK5 immunoprecipitates from fibroblast lysates contained ERK3 immunoreactivity. Proximity ligation assays revealed ERK3‐MK5 complexes in the cytoplasm, which were less abundant following knockdown of MK5. ERK3‐MK5 complexes were not observed in the nucleus. Cell migration, in response to serum and/or angiotensin II, was reduced upon siRNA‐mediated knockdown of ERK3. However, whereas the secretion of type 1 collagen and fibronectin was increased in MK5 −/− or MK5‐kd cells relative to MK5 +/+ fibroblasts, knocking down ERK3 did not affect collagen secretion. Conclusion MK5 and ERK3 immunoreactivity was detected in fibroblasts but not myocytes. Co‐immunoprecipitation and PLA suggest that ERK3 and MK5 form cytoplasmic complexes in cardiac fibroblasts. Suppressing ERK3 or MK5 expression decreased cell motility; however, type 1 collagen secretion was enhanced by reduced MK5 expression but unaffected by knockdown of ERK3. Hence, MK5 and ERK3 play overlapping but distinct roles in regulating cardiac fibroblast function. Support or Funding Information This study was supported by a grant from the Heart and Stroke Foundation of Canada. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| 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) | 0,001 | 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 source (Gemma direct ou Codex distillé), 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 ».