Identification of axon growth promoters in the secretome of the deer antler velvet. (6th January 2017)

• Record Type: Journal Article
• Authors: Pita-Thomas, Wolfgang; Barroso-García, Gemma; Moral, Veronica; Hackett, Amber R.; Cavalli, Valeria; Nieto-Diaz, Manuel
• Is Part Of: Neuroscience. Volume 340(2017)
• Page Start: 333
• Page End: 344
• Publication Date: 2017-01-06
• Subjects: ACN acetonitrile -- ANOVA analysis of variance -- BW body weight -- ECM extracellular matrix -- EDTA ethylenediaminetetraacetic acid -- ELISA enzyme linked immunosorbent assay -- FA formic acid -- FBS fetal bovine serum -- IDA Information Dependent Acquisition -- MWCO molecular weight cutoff -- NGF nerve growth factor -- PBS phosphate-buffered saline -- PLL poly-l-lysine -- SDS–PAGE sodium dodecyl sulfate–polyacrylamide gel electrophoresis -- SRM selected reaction monitoring -- VCM velvet-conditioned medium; peripheral nervous system -- axon regeneration -- deer antler -- secreted proteins -- proteomics; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.10.063
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Antler velvet secretes proteins that promote neurite growth in trigeminal neurons. Skin promotes neurite growth solely using NGF while velvet uses additional proteins. Velvet secretes more than 20 axon growth promoters including NGF and periostin. Periostin and NGF synergistically promote neurite growth mimicking velvet's effect. Abstract: Every spring, deer cast their old antlers and initiate a regeneration process, which yields a new set of antlers of up to 1 m in length. Over the course of three months, branches of the trigeminal nerve, originating from the frontal skull, innervate velvet, a modified skin that covers the regenerating antler. The rate of growth of these axons reaches up to 2 cm per day making them the fastest regenerating axons in adult mammals. Here, we aim to identify the factors secreted by velvet that promote such high speed axon growth. Our experiments with cultures of adult rat trigeminal neurons demonstrate that conditioned medium harvested from velvet organotypic cultures has greater axon growth-promoting properties than a medium conditioned by normal skin. The axon growth-promoting effects of velvet act synergistically with the extracellular matrix (ECM) protein laminin, a component of the basal lamina present in the deer antler. Our proteomic analyses identified several axon growth promoters in the velvet-conditioned medium (VCM), including soluble proteins such as nerve growth factor (NGF) and apolipoprotein A-1, as well as matrix extracellular proteins, such as periostin and SPARC. Additional in vitro analyses allowed us to determine that a synergic relationship between periostin and NGF may contribute to neurite growth-promoting effects of velvet secretome. A combinatorial approach using these factors may promote regeneration at high speeds in patients with peripheral neuropathies.