Preclinical studies on anti-fibrotic effects of Neuregulin-1

Fibrosis plays a role in the pathogenesis of many chronic diseases and is a central feature in specific disorders including scleroderma, lung fibrosis, and liver cirrhosis. There is currently no effective treatment available that halts development of fibrosis. Recently obtained preliminary data in our laboratory show that Neuregulin-1 (NRG-1) decreases fibrosis in a bleomycin-induced model of skin fibrosis. Based on these preliminary data, we hypothesize that NRG-1 plays a central – but unexplored – role in extracellular matrix biology and fibrotic diseases. NRG-1 is a proteins that plays a crucial role in development of neural and cardiovascular systems, but with an unknown role in fibrosis. The aim of this project is to confirm and expand on the in vivo anti-fibrotic effects of NRG-1 by looking at expression of extracellular matrix proteins and inflammatory cytokines. Furthermore, we will check the anti-fibrotic effects of NRG-1 on isolated fibroblasts to discriminate between direct and indirect effects. Finally, we will perform a micro-array experiment on isolated fibroblasts with or without stimulation with NRG-1 to uncover the signaling pathways involved in the anti-fibrotic effects of NRG-1. The proposed experiments will help us to confirm and expand on the preliminary findings and to determine the underlying antifibrotic pathways.

Keywords:NEUREGULIN-1, FIBROSIS

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Physiology, Regenerative medicine, Other basic sciences, Other clinical sciences, Other health sciences, Nursing, Other paramedical sciences, Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences, Other translational sciences, Other medical and health sciences