HIP-55/DBNL-dependent regulation of adrenergic receptor mediates the ERK1/2 proliferative pathway

Abstract

The activation of β-adrenergic receptors (β-ARs) plays a key role in regulating cardiac function. However, the detailed regulatory mechanisms of β-AR-induced fibrosis are still unclear. We used a proteomics approach to analyze the changes in protein expression patterns in cardiac fibrosis with β-AR stimulation. HIP-55 (also called debrin-like; DBNL) was revealed as a novel regulator in the signaling regulatory network with β-AR activation. Further studies of both HIP-55-overexpressed and -deficient cardiac fibroblasts indicated that HIP-55 negatively regulated β-AR-activated cardiac fibroblast proliferation and the proliferative signaling pathway may be associated with the extracellular signal-regulated protein kinase (ERK) activation. Our data provide a new mechanistic insight into the role of HIP-55 in β-AR-induced cardiac fibroblast proliferation and suggest a new treatment strategy for proliferative disorders.