The occurrence of airway epithelial thickening in asthma

The occurrence of airway epithelial thickening in order Embelin leads to a decrease in airway lumen size, consequently resulting in increased airway resistance corresponding to AHR (Elias, Zhu, Chupp, and Homer, 1999). Data from pediatric and non-fatal asthma studies have shown epithelial thickness of the airways can increase 2-fold (James, Maxwell, Pearce-Pinto, Elliot, and Carroll, 2002; Kim et al., 2007), which is consistent with current findings in the study that demonstrated OVA-challenged mice had a clear significant increase in epithelial thickness as compared to saline-treated controls. The finding that MSCs were unable to reduce epithelial thickness is consistent with past studies using i.v tail vein injections of MSCs in OVA-injured mice with chronic AAD (Bonfield et al., 2010), whereas the ability of RLN to reverse epithelial thickness is consistent with its previously reported effects in the AAD model (Royce et al., 2014; Royce et al., 2009). These findings may explain 1) why RLN, but not MSCs, was able to reduce AHR (as only RLN decreased both epithelial thickness and airway/lung fibrosis, which both contribute to AHR); and 2) perhaps why the combined effects of MSCs and RLN did not further reduce AHR beyond that reversed by RLN alone (as the combination treatment was not able to reverse epithelial thickness beyond that induced by RLN alone). This would suggest that reducing both the originating epithelial damage, activation and thickening on top of the subsequent airway/lung fibrosis may better protect from AAD-induced AWR and the contributions of.
Acknowledgments We sincerely thank Mr. Junli (Vingo) Zhuang for maintaining the MSCs required for the outlined studies. This work was supported in part by a Monash University MBio Postgraduate Discovery Scholarship (MPDS) to Krupesh P. Patel; a Kidney Health Australia Medical and Science Research Scholarship to Brooke M. Huuskes; and a National Health & Medical Research Council (NHMRC) of Australia Senior Research Fellowship (GNT1041766) to Chrishan S. Samuel.
Introduction In the adult mammalian brain, stem and precursor cells localize close to vasculature in two distinct niches, the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricles (Palmer et al., 2000). Although neurogenesis in the SGZ can be increased by systemic interventions like environmental enrichment, physical activity and exploratory behavior (Freund et al., 2013; Kempermann et al., 1997; Kronenberg et al., 2003; Van Praag et al., 1999), and can be down-regulated by stress (Schoenfeld and Gould, 2013), we lack detailed information on how exactly such systemic changes are conveyed to the neurogenic precursor cells in the niche. The niche concept of stem cell biology proposes that stem cells require local environmental cues to control self-renewal and differentiation (Guilak et al., 2009; Scadden, 2006). In the hippocampus, this mediation will take place at several levels (Kempermann, 2011), presumably in parallel and in an interactive manner, involving direct cell-to-cell signaling via gap-junctions (Kunze et al., 2009), paracrine signals such as Wnt (Lie et al., 2005), neurotransmitters, most notably glutamate (Cameron et al., 1995) and GABA (Ge et al., 2006; Wang et al., 2005), as well as systemic factors, including growth factors and hormones. A number of studies have addressed the same issue for the SVZ. Lim and Alvarez-Buylla first described the close interaction of astrocytes and neural precursor cells in the SVZ niche (Lim and Alvarez-Buylla, 1999), which paralleled the discovery by the same group that the precursor cells actually have astrocyte-like properties themselves (Doetsch et al., 1999), also in the human brain (Sanai et al., 2004). That group also highlighted the lineage-relationship between astrocyte-like precursor cells and the generation of oligodendrocytes in the SVZ (Menn et al., 2006). Whereas in the SGZ a small number of new oligodendrocytes is found (Kempermann et al., 2003), these originate from a different set of precursor cells than the neurons and astrocytes. Nevertheless, our precursor cell cultures reveal potency for neuronal, astrocytic and oligodendrocytic lineages (Babu et al., 2011), although extremely few oligodendrocytes are produced. They are thus not routinely assessed in our assays, especially given the fact that they are of different origin in vivo under normal condition. Their production can, however, be induced by overexpression of Ascl1 in intermediate progenitor cells (Jessberger et al., 2008).