Dopamine Receptor Control of Collagen Transcription and Secretion: Relevance to Fibrosis, Health and Disease

Abstract

Dopamine receptors (DRs) play critical roles beyond the central nervous system, influencing cardiovascular function and fibrosis. However, the impact of DR signaling on collagen regulation in cardiac fibroblasts remains poorly understood, specifically the direct and indirect effects on collagen transcription factors. SP1, SMAD3, and TCF21 are all important transcription factors, previously determined in Endothelin-1 (ET1), Angiotensin II (Ang II), and transforming growth factor beta-1 (TGFb-1) pathways for collagen synthesis and accumulation. This study aims to investigate the effects of dopamine receptor 1 (D1R) and dopamine receptor 3 (D3R) signaling on transcription factors mediated by these established collagen synthesis pathways in regulation of human fibroblasts, that are heavily involved in health and disease across the human body, especially the cardiovascular system. By elucidating the role of dopamine receptor signaling in regulating collagen transcription and secretion, this study will provide insights into novel cellular and nuclear mechanisms underlying fibrosis in cardiovascular disease. Moreover, since collagen regulation is critical for tissue remodeling, wound healing, and fibrotic disorders beyond the cardiovascular system, these findings may have broader implications for human health and disease.