2024-01-24 デューク大学(Duke)
◆これは心臓の再生に道を開く可能性があり、心筋損傷の治療法の新しい方向性を提供する可能性があります。しかし、実験結果は一部の制約があり、遺伝子活性化の投与量と期間を厳密に制御する必要があることが示唆されています。将来的な治療法の開発には、遺伝子を正確な細胞に届けるための異なるデリバリーシステムの開発や、心臓組織の再生を促進する方法の研究が必要です。
<関連情報>
- https://pratt.duke.edu/news/skin-cancer-genes-heal-hearts/
- https://www.science.org/doi/10.1126/sciadv.adh2598
BRAF-V600Eが人工心筋の細胞周期、代謝、機能に及ぼす時間依存的影響 Time-dependent effects of BRAF-V600E on cell cycling, metabolism, and function in engineered myocardium
NICHOLAS STRASH , SOPHIA DELUCA , GEOVANNI L. JANER CARATTINI , YIFAN CHEN , […], AND NENAD BURSAC
Science Advances Published:24 Jan 2024
DOI:https://doi.org/10.1126/sciadv.adh2598
Abstract
Candidate cardiomyocyte (CM) mitogens such as those affecting the extracellular signal–regulated kinase (ERK) signaling pathway represent potential targets for functional heart regeneration. We explored whether activating ERK via a constitutively active mutant of B-raf proto-oncogene (BRAF), BRAF-V600E (caBRAF), can induce proproliferative effects in neonatal rat engineered cardiac tissues (ECTs). Sustained CM-specific caBRAF expression induced chronic ERK activation, substantial tissue growth, deficit in sarcomeres and contractile function, and tissue stiffening, all of which persisted for at least 4 weeks of culture. caBRAF-expressing CMs in ECTs exhibited broad transcriptomic changes, shift to glycolytic metabolism, loss of connexin-43, and a promigratory phenotype. Transient, doxycycline-controlled caBRAF expression revealed that the induction of CM cycling is rapid and precedes functional decline, and the effects are reversible only with short-lived ERK activation. Together, direct activation of the BRAF kinase is sufficient to modulate CM cycling and functional phenotype, offering mechanistic insights into roles of ERK signaling in the context of cardiac development and regeneration.
