Limb-bud and Heart (LBH) mediates proliferation, fibroblast-to-myofibroblast transition and EMT-like processes in cardiac fibroblasts.
CRYAB
Cardiac fibroblasts
Fibroblast-to-myofibroblast transition
LBH
TGF-β1
Journal
Molecular and cellular biochemistry
ISSN: 1573-4919
Titre abrégé: Mol Cell Biochem
Pays: Netherlands
ID NLM: 0364456
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
16
10
2020
accepted:
12
02
2021
pubmed:
6
3
2021
medline:
28
7
2021
entrez:
5
3
2021
Statut:
ppublish
Résumé
Cardiac fibrosis is an important pathological change after myocardial infarction (MI). Its progression is essential for post-MI infarct healing, during which transforming growth factor beta1 (TGF-β1) plays a critical role. Limb-bud and Heart (LBH), a newly discovered target gene of TGF-β1, was shown to promote normal cardiogenesis. αB-crystallin (CRYAB), an LBH-interacting protein, was demonstrated to be involved in TGF-β1-induced fibrosis. The roles and molecular mechanisms of LBH and CRYAB during cardiac fibrosis remain largely unexplored. In this study, we investigated the alterations of LBH and CRYAB expression in mouse cardiac tissue after MI. LBH and CRYAB were upregulated in activated cardiac fibroblasts (CFs), while in vitro TGF-β1 stimulation induced the upregulation of LBH, CRYAB, and fibrogenic genes in primary CFs of neonatal rats. The results of the ectopic expression of LBH proved that LBH accelerated CF proliferation under hypoxia, mediated the expression of CRYAB and fibrogenic genes, and promoted epithelial-mesenchymal transition (EMT)-like processes in rat CFs, while subsequent CRYAB silencing reversed the effects induced by elevated LBH expression. We also verified the protein-protein interaction (PPI) between LBH and CRYAB in fibroblasts. In summary, our work demonstrated that LBH promotes the proliferation of CFs, mediates TGF-β1-induced fibroblast-to-myofibroblast transition and EMT-like processes through CRYAB upregulation, jointly functioning in post-MI infarct healing. These findings suggest that LBH could be a promising potential target for the study of cardiac repair and cardiac fibrosis.
Identifiants
pubmed: 33666830
doi: 10.1007/s11010-021-04111-7
pii: 10.1007/s11010-021-04111-7
doi:
Substances chimiques
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2685-2701Subventions
Organisme : National Natural Science Foundation of China
ID : No. 31771060
Organisme : National Natural Science Foundation of China
ID : No. U1501222
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