βIV-Spectrin/STAT3 complex regulates fibroblast phenotype, fibrosis, and cardiac function.

ABSTRACT: Increased fibrosis is a characteristic remodeling response to biomechanical and neurohumoral stress and a determinant of cardiac mechanical and electrical dysfunction in disease. Stress-induced activation of cardiac fibroblasts (CFs) is a critical step in the fibrotic response, although the precise sequence of events underlying activation of these critical cells in vivo remain unclear. Here, we tested the hypothesis that a βIV-spectrin/STAT3 complex is essential for maintenance of a quiescent phenotype (basal nonactivated state) in CFs. We reported increased fibrosis, decreased cardiac function, and electrical impulse conduction defects in genetic and acquired mouse models of βIV-spectrin deficiency. Loss of βIV-spectrin function promoted STAT3 nuclear accumulation and transcriptional acti

SUBMITTER: Patel NJ 

PROVIDER: S-EPMC6824442 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature