Background: Mature cardiomyocytes are unable to proliferate, preventing the injured adult heart from repairing itself. Studies in rodents have suggested that the extracellular matrix protein agrin promotes cardiomyocyte proliferation in the developing heart and that agrin expression is downregulated shortly after birth, resulting in the cessation of proliferation. Agrin based therapies have proven successful at inducing repair in animal models of cardiac injury, however whether similar pathways exist in the human heart is unknown.
Methods: Right ventricular (RV) biopsies were collected from 40 patients undergoing surgery for congenital heart disease and the expression of agrin and associated proteins was investigated.
Results: Agrin transcripts were found in all samples and their levels were significantly negatively correlated to age ( = 0.026), as were laminin transcripts ( = 0.023), whereas no such correlation was found for the other proteins analyzed. No significant correlations for any of the proteins were found when grouping patients by their gender or pathology. Immunohistochemistry and western blots to detect and localize agrin and the other proteins under analysis in RV tissue, confirmed their presence in patients of all ages.
Conclusions: We show that agrin is progressively downregulated with age in human RV tissue but not as dramatically as has been demonstrated in mice; highlighting both similarities and differences to findings in rodents. Our results lay the groundwork for future studies exploring the potential of agrin-based therapies in the repair of damaged human hearts.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959542 | PMC |
| http://dx.doi.org/10.3389/fcvm.2022.813904 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Regulation of miR-206 in denervated and dystrophic muscles, and its effect on acetylcholine receptor clustering.
J Cell Sci
December 2024
Department of Molecular, Cellular and Developmental Biology, 1105 N. University Avenue, Ann Arbor, MI 48109, USA.
The muscle-specific microRNA miR-206 has recently emerged as a potential regulator of genes involved in the formation and regeneration of the neuromuscular junction (NMJ). This study investigated miR-206-3p (miR-206) expression in synaptic and non-synaptic regions of denervated mice and α-dystrobrevin (Dtna)-knockout mice, as well as its impact on the formation and/or maintenance of agrin-induced acetylcholine receptor (AChR) clusters. In denervated, Dtna-deficient and crushed muscles, miR-206 expression significantly increased compared to what was seen for innervated muscles.
View Article and Find Full Text PDFAcute high-intensity muscle contraction moderates AChR gene expression independent of rapamycin-sensitive mTORC1 pathway in rat skeletal muscle.
Exp Physiol
January 2025
Graduate School of Health and Sport Science, Nippon Sport Science University, Tokyo, Japan.
Article Synopsis
- The study investigates how intense electrical muscle contractions, simulating resistance exercise, affect the expression of acetylcholine receptor (AChR) genes and related signaling pathways in rats.
- Early recovery showed changes in Agrn and LRP4 gene expressions, while late recovery impacted multiple AChR-related genes and increased protein levels for agrin and MuSK.
- Importantly, the changes in AChR subunit expressions post-muscle contraction were found to be independent of the mTORC1 signaling pathway, despite mTORC1 activity in the early recovery phase.
Grilled nux vomica alleviates myasthenia gravis by inhibiting the JAK2/STAT3 signaling pathway: a study in a mice model.
Eur J Med Res
October 2024
Department of Neurology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), No.54 Youdian Road, Hangzhou, 310006, Zhejiang Province, China.
Article Synopsis
- Grilled Nux Vomica (GNV) shows promise as a treatment for myasthenia gravis (MG), but further research is needed to fully understand its effects and mechanisms.
- GNV significantly improved various health metrics (body weight, muscle strength, clinical scores) in a mouse model of autoimmune MG and also reduced inflammatory markers and protected neuromuscular junctions in a dose-dependent manner.
- Co-treatment with JAK2 and STAT3 inhibitors enhanced GNV's beneficial effects, suggesting that inhibiting the JAK2/STAT3 pathway could be an effective strategy for MG treatment.
Changes in muscle quality and biomarkers of neuromuscular junctions and muscle protein turnover following 12 weeks of resistance training in older men.
Biol Sport
October 2024
Faculty of Physical Education, Jozef Pilsudski University of Physical Education in Warsaw, Warsaw, Poland.
The present study aimed to investigate the effects of 12 weeks of resistance training (RT) on body composition [fat mass (FM), lean body mass (LBM)], muscle quality upper and lower (MQU, MQL), muscle size [cross sectional area (CSA), quadriceps cross-sectional area (QCSA)], biomarkers of neuromuscular junctions [C-terminal agrin fragment (CAF)], and muscle protein turnover [N-terminal peptide (P3NP), 3-methylhistidine (3MH), skeletal muscle-specific isoform of troponin T (sTnT)] in older men. Thirty elderly men (age 66.23 ± 0.
View Article and Find Full Text PDFMolecular basis of proteolytic cleavage regulation by the extracellular matrix receptor dystroglycan.
Structure
November 2024
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA. Electronic address:
Article Synopsis
- The dystrophin-glycoprotein-complex (DGC), which connects the cell's internal structure to its external environment, is crucial for muscle function, and its disruption is linked to diseases like muscular dystrophy.
- Recent research focused on understanding how matrix-metalloproteinases (MMPs) can cleave dystroglycan, a key protein in the DGC, and how this might contribute to such diseases.
- By analyzing the structure of dystroglycan, scientists discovered how its unique C-terminal extension regulates MMP cleavage, which could help clarify mechanisms behind DGC disruption in muscular dystrophy.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!