Peripheral Nerve Pericytes Modify the Blood-Nerve Barrier Function and Tight Junctional Molecules Through the Secretion of Various Soluble Factors

Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Journal of Cellular Physiology (Impact Factor: 3.84). 01/2011; 226(1):255-66. DOI: 10.1002/jcp.22337
Source: PubMed


The objectives of this study were to establish pure blood-nerve barrier (BNB) and blood-brain barrier (BBB)-derived pericyte cell lines of human origin and to investigate their unique properties as barrier-forming cells. Brain and peripheral nerve pericyte cell lines were established via transfection with retrovirus vectors incorporating human temperature-sensitive SV40 T antigen (tsA58) and telomerase. These cell lines expressed several pericyte markers such as α-smooth muscle actin, NG2, platelet-derived growth factor receptor β, whereas they did not express endothelial cell markers such as vWF and PECAM. In addition, the inulin clearance was significantly lowered in peripheral nerve microvascular endothelial cells (PnMECs) through the up-regulation of claudin-5 by soluble factors released from brain or peripheral nerve pericytes. In particular, bFGF secreted from peripheral nerve pericytes strengthened the barrier function of the BNB by increasing the expression of claudin-5. Peripheral nerve pericytes may regulate the barrier function of the BNB, because the BNB does not contain cells equivalent to astrocytes which regulate the BBB function. Furthermore, these cell lines expressed several neurotrophic factors such as NGF, BDNF, and GDNF. The secretion of these growth factors from peripheral nerve pericytes might facilitate axonal regeneration in peripheral neuropathy. Investigation of the characteristics of peripheral nerve pericytes may provide novel strategies for modifying BNB functions and promoting peripheral nerve regeneration.

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Available from: Tetsuya Terasaki, Jul 17, 2015
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    • "Again, whether selective ablation of pericytes from skeletal muscle will prevent or otherwise affect regeneration will clarify whether they can be replaced by other cell types with myogenic capacity. We propose that due to their ability to secrete several growth factors, pericytes may be required to induce other cell types to adopt a myogenic fate (Sato and Rifkin, 1989; Shepro and Morel, 1993; Davis et al., 1996; Yamagishi et al., 1999; Brown et al., 2001; Reinmuth et al., 2001; Hirschi et al., 2003; Niimi, 2003; Armulik et al., 2005; Paquet- Fifield et al., 2009; Shimizu et al., 2011). A global analysis of candidate growth factors secreted by skeletal muscle pericytes that promote skeletal muscle regeneration is required. "
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    ABSTRACT: Pericytes are perivascular cells that envelop and make intimate connections with adjacent capillary endothelial cells. Recent studies show that they may have a profound impact in skeletal muscle regeneration, innervation, vessel formation, fibrosis, fat accumulation, and ectopic bone formation throughout life. In this review, we summarize and evaluate recent advances in our understanding of pericytes' influence on adult skeletal muscle pathophysiology. We also discuss how further elucidating their biology may offer new approaches to the treatment of conditions characterized by muscle wasting.
    Frontiers in Aging Neuroscience 09/2014; 6:245. DOI:10.3389/fnagi.2014.00245 · 4.00 Impact Factor
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    • "We have shown that αSMA positive pericytes secrete chemokines and cytokines into media in response to pro-inflammatory cues in the absence of microglia or astrocytes. Other groups have also shown that pericytes can secrete factors that are essential for proper BBB functioning and can affect gene and protein expression in surrounding endothelial cells [78,79]. Co-culture studies of brain pericytes and endothelial cells indicate an important role in maintenance of hemostasis as well as BBB permeability to pathogens, such as HIV-1, in human and mouse cells, respectively [80,81]. "
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    • "Rare pathological studies have reported perivascular lymphocytic infiltration in the endoneurial microvessels of the BNB [9–12]. The presence of circulating cytokines, such as VEGF, TNF-α, and IL-1β, appears to be linked to dysfunction of the BNB in MMN patients [37]. A recent study using an in vitro BNB model, consisting of conditionally immortalised human BNB-derived endothelial cells, has suggested that VEGF is the main effector molecule linked to the pathogenesis of the BNB breakdown [38]. "
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