Systems analysis reveals neuregulin-1 control of cardiomyocyte size and shape mediated by distinct PI3K and p38 pathways.

ABSTRACT: Cardiac hypertrophy is a common precursor to heart failure, but its cellular manifestations-changes in cardiomyocyte size and shape-are regulated by poorly understood signaling networks. Here, we combined high-content morphological profiling, proteomics, and systems modeling to characterize the diverse forms of hypertrophy induced by angiotensin II, endothelin-1, insulin growth factor-1, and neuregulin-1 (Nrg1). Reverse-phase protein array profiling and partial least squares regression modeling revealed that AKT, GSK3, and MAPK signaling are differentially regulated by hypertrophic agonists and are predictive of distinct phenotypic outcomes. Nrg1 uniquely induced cardiomyocyte elongation in both neonatal rat and human iPSC-derived cardiomyocytes, in addition to increasing cell area. Pharma

SUBMITTER: Luanpaisanon P 

PROVIDER: S-EPMC12621799 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature