The affect of N-Cadherin on cardiac regeneration and its therapeutic potential to revive myocardial perform following harm. Credit score: Nationwide Taiwan College
Grownup human hearts possess restricted regenerative talents, so dropping cardiomyocytes (CMs) after harm may end up in contractile dysfunction and coronary heart failure. In distinction, neonatal mammalian hearts can regenerate, although the underlying molecular mechanisms stay unclear.
By way of comparative transcriptome evaluation, Professor Kai-Chien Yang’s group recognized the adherens junction protein N-Cadherin as a key regulator of CM proliferation and renewal. Its expression, which correlates positively with mitotic gene exercise, decreases with age. The examine is revealed in Nature Communications.
In neonatal mice, harm induces a rise in N-Cadherin ranges that coincides with enhanced CM mitosis. Experimentally, decreasing N-Cadherin expression diminishes CM proliferation in each neonatal mouse hearts and human-induced pluripotent stem cell-derived CMs, whereas overexpressing it boosts proliferation.
Mechanistic research reveal that N-Cadherin interacts with and stabilizes the pro-mitotic transcription regulator β-Catenin, thereby driving CM self-renewal.
As well as, focused deletion of N-Cadherin in CMs impairs cardiac regeneration in neonatal mice, resulting in extreme scarring, whereas its overexpression promotes regeneration in grownup mouse hearts following ischemic harm.
“These findings suggest that targeting N-Cadherin could be a promising strategy for enhancing cardiac regeneration and restoring function in injured adult human hearts,” Professor Yang says. “And this may offer hope for improving outcomes for heart failure patients.”
Extra info:
Yi-Wei Tsai et al, N-Cadherin promotes cardiac regeneration by potentiating pro-mitotic β-Catenin signaling in cardiomyocytes, Nature Communications (2025). DOI: 10.1038/s41467-025-56216-y
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Therapeutic the damaged coronary heart: How a key junctional protein could unlock the potential of cardiac regeneration (2025, February 24)
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