Versican (VCAN) proteolysis and the accumulation of VCAN fragments occur in many developmental and disease processes, affecting extracellular matrix (ECM) structure and cell phenotype. Little is known about the significance of proteolysis and the roles of fragments, or how this ECM remodeling affects the microenvironment and phenotype of diseased cells. G1-DPEAAE fragments promote aspects of epithelial–mesenchymal transitioning in developing and diseased cells, resulting in cell migration. Enhanced proliferation and invasion of tumor and endothelial cells is directly associated with G1 domain deposition and G1-DPEAAE localization respectively. These tumorigenic and angiogenic roles could explain the disease exacerbating effect often associated with G1-containing fragments, however, the pathogenicity of G1 fragments depends entirely upon the context. Overall, VCAN fragments promote tumorigenesis and inflammation; however, the specific cleavage site, the extent of cleavage activity and the microenvironment in which cleavage occurs collectively determine how this pleiotropic molecule and its fragments influence cells.
Pituitary adenylate cyclase‐activating polypeptide (PACAP) is an important regulator of the stress response in mammals, influencing both the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system (SNS). PACAP has been reported to influence energy homeostasis, including adaptive thermogenesis, an energy burning process in adipose tissue regulated by the SNS in response to cold stress and overfeeding. While research suggests PACAP acts centrally at the level of the hypothalamus, knowledge of PACAP's role within the sympathetic nerves innervating adipose tissues in response to metabolic stressors is limited. This work shows, for the first time, gene expression of PACAP receptors in stellate ganglia and highlights some differential expression with housing temperature. Additionally, we present our dissection protocol, analysis of tyrosine hydroxylase gene expression as a molecular biomarker for catecholamine producing tissue and recommend three stable reference genes for the normalization of quantitative real time‐polymerase chain reaction (qRT‐PCR) data when working with this tissue. This study adds to information about neuropeptide receptor expression in peripheral ganglia of the sympathetic nervous system innervating adipose tissue and provides insight into PACAP's role in the regulation of energy metabolism.
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