Pre-existing fibroblasts of epicardial origin are the primary source of pathological fibrosis in cardiac ischemia and aging.

Serum response factor (SRF) and the SRF co-activators myocardin-related transcription factors (MRTFs) are essential for epicardium-derived progenitor cell (EPDC)-mobilization during heart development; however, the impact of developmental EPDC deficiencies on adult cardiac physiology has not been evaluated. Here, we utilize the Wilms Tumor-1 (Wt1)-Cre to delete Mrtfs or Srf in the epicardium, which reduced the number of EPDCs in the adult cardiac interstitium. Deficiencies in Wt1-lineage EPDCs prevented the development of cardiac fibrosis and diastolic dysfunction in aged mice.

Exercise promotes a cardioprotective gene program in resident cardiac fibroblasts.

Exercise and heart disease both induce cardiac remodeling, but only disease causes fibrosis and compromises heart function. The cardioprotective benefits of exercise have been attributed to changes in cardiomyocyte physiology, but the impact of exercise on cardiac fibroblasts (CFs) is unknown. Here, RNA-sequencing reveals rapid divergence of CF transcriptional programs during exercise and disease.

Epicardial Outgrowth Culture Assay and Ex Vivo Assessment of Epicardial-derived Cell Migration.

A single layer of epicardial cells lines the heart, providing paracrine factors that stimulate cardiomyocyte proliferation and directly contributing cardiovascular progenitors during development and disease. While a number of factors have been implicated in epicardium-derived cell (EPDC) mobilization, the mechanisms governing their subsequent migration and differentiation are poorly understood. Here, we present in vitro and ex vivo strategies to study EPDC motility and differentiation.

Myocardin-related transcription factors control the motility of epicardium-derived cells and the maturation of coronary vessels.

An important pool of cardiovascular progenitor cells arises from the epicardium, a single layer of mesothelium lining the heart. Epicardium-derived progenitor cell (EPDC) formation requires epithelial-to-mesenchymal transition (EMT) and the subsequent migration of these cells into the sub-epicardial space. Although some of the physiological signals that promote EMT are understood, the functional mediators of EPDC motility and differentiation are not known.

Activation of MRTF-A-dependent gene expression with a small molecule promotes myofibroblast differentiation and wound healing.

Myocardin-related transcription factors (MRTFs) regulate cellular contractility and motility by associating with serum response factor (SRF) and activating genes involved in cytoskeletal dynamics. We reported previously that MRTF-A contributes to pathological cardiac remodeling by promoting differentiation of fibroblasts to myofibroblasts following myocardial infarction. Here, we show that forced expression of MRTF-A in dermal fibroblasts stimulates contraction of a collagen matrix, whereas contractility of MRTF-A null fibroblasts is impaired under basal conditions and in response to TGF-β1 stimulation.

Intranasal delivery of Norwalk virus-like particles formulated in an in situ gelling, dry powder vaccine.

The development of a vaccine to prevent norovirus infections has been focused on immunization at a mucosal surface, but has been limited by the low immunogenicity of self-assembling Norwalk virus-like particles (NV VLPs) delivered enterically or at nasal surfaces. Nasal immunization, which offers the advantage of ease of immunization, faces obstacles imposed by the normal process of mucociliary clearance, which limits residence time of applied antigens. Herein, we describe the use of a dry powder formulation (GelVac) of an inert in situ gelling polysaccharide (GelSite) extracted from Aloe vera for nasal delivery of NV VLP antigen.

An intranasally delivered Toll-like receptor 7 agonist elicits robust systemic and mucosal responses to Norwalk virus-like particles.

Norwalk virus (NV) is an enteric pathogen from the genus Norovirus and a major cause of nonbacterial gastroenteritis in humans. NV virus-like particles (VLPs) are known to elicit systemic and mucosal immune responses when delivered nasally; however, the correlates of immune protection are unknown, and codelivery with a safe and immunogenic mucosal adjuvant may enhance protective anti-NV immune responses. Resiquimod (R848), an imidazoquinoline-based Toll-like receptor 7 and/or 8 (TLR7/8) agonist, is being evaluated as an adjuvant in FDA-approved clinical vaccine trials.

Differential regulation of transferrin 1 and 2 in Aedes aegypti.

Available evidence has shown that transferrins are involved in iron metabolism, immunity and development in eukaryotic organisms including insects. Here we characterize the gene and message expression profile of Aedes aegypti transferrin 2 (AaTf2) in response to iron, bacterial challenge and life stage. We show that AaTf2 shares a low similarity with A.