<i>Nicotinic receptor signaling in nonexcitable epithelial cells: paradigm shifting from ion current to kinase cascade.</i> Focus on “Upregulation of nuclear factor-κB expression by SLURP-1 is mediated by α<sub>7</sub>-nicotinic acetylcholine receptor and involves both ionic events and activation of protein kinases”

Slominski, Andrzej

doi:10.1152/ajpcell.00324.2010

Cited by 6 publications

(4 citation statements)

References 34 publications

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“…These findings provide insight into an element of host defense previously unknown to contribute to the BBB integrity and cBMEC shedding, but the implications of the cholinergic α7 nAChR pathway for the pathogenesis and therapeutics of BBB disorders and CNS inflammation remain to be explored. Alpha7 nAChR has been found to be able to mediate SLURP (secreted mammalian Ly-6/urokinase plasminogen activator receptor-related protein)-1-upregulated NF-κB through both ionic events (calcium signaling) and activation of protein kinases [57]. Both UCHL1 and S100B are shown to be involved in regulation of NF-κB [49], [52], [58].…”

Section: Discussionmentioning

confidence: 99%

Circulating Brain Microvascular Endothelial Cells (cBMECs) as Potential Biomarkers of the Blood–Brain Barrier Disorders Caused by Microbial and Non-Microbial Factors

et al. 2013

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Despite aggressive research, central nervous system (CNS) disorders, including blood-brain barrier (BBB) injury caused by microbial infection, stroke, abused drugs [e.g., methamphetamine (METH) and nicotine], and other pathogenic insults, remain the world's leading cause of disabilities. In our previous work, we found that dysfunction of brain microvascular endothelial cells (BMECs), which are a major component of the BBB, could be caused by nicotine, meningitic pathogens and microbial factors, including HIV-1 virulence factors gp41 and gp120. One of the most challenging issues in this area is that there are no available cell-based biomarkers in peripheral blood for BBB disorders caused by microbial and non-microbial insults. To identify such cellular biomarkers for BBB injuries, our studies have shown that mice treated with nicotine, METH and gp120 resulted in increased blood levels of CD146+(endothelial marker)/S100B+ (brain marker) circulating BMECs (cBMECs) and CD133+[progenitor cell (PC) marker]/CD146+ endothelial PCs (EPCs), along with enhanced Evans blue and albumin extravasation into the brain. Nicotine and gp120 were able to significantly increase the serum levels of ubiquitin C-terminal hydrolase 1 (UCHL1) (a new BBB marker) as well as S100B in mice, which are correlated with the changes in cBMECs and EPCs. Nicotine- and meningitic E. coli K1-induced enhancement of cBMEC levels, leukocyte migration across the BBB and albumin extravasation into the brain were significantly reduced in alpha7 nAChR knockout mice, suggesting that this inflammatory regulator plays an important role in CNS inflammation and BBB disorders caused by microbial and non-microbial factors. These results demonstrated that cBMECs as well as EPCs may be used as potential cell-based biomarkers for indexing of BBB injury.

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Section: Discussionmentioning

confidence: 99%

Circulating Brain Microvascular Endothelial Cells (cBMECs) as Potential Biomarkers of the Blood–Brain Barrier Disorders Caused by Microbial and Non-Microbial Factors

et al. 2013

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“…The ACh signaling network of the corneal epithelium is an example of the more general neuroendocrine-like mechanisms that mediate peripheral responses to environmental factors and of evolutionary conservation of neuroendocrine systems in the periphery [6,7]. ACh is produced by practically all types of living cells [8], and its concentration is remarkably high in the corneal epithelium, even exceeding that in the neural tissue (reviewed in [9]).…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of synergy of corneal muscarinic and nicotinic acetylcholine receptors in upregulation of E-cadherin expression

Chernyavsky

Galitovskiy

Grando

2015

International Immunopharmacology

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“…SLURP‐1 has been identified in the studies of the autosomal recessive keratotic palmoplantar skin disorder Mal de Meleda that features inactivation of SLURP‐1 through point mutation. SLURP‐1 has been detected in neurons, respiratory, and digestive epithelia, cornea, fibroblasts, lymphocytes, uterus, and bone (reviewed in). SLURP‐2 was discovered during microarray analysis of novel genes whose expression in skin samples of patients with psoriasis was predominantly increased .…”

Section: Introductionmentioning

confidence: 99%

Novel cholinergic peptides SLURP‐1 and ‐2 regulate epithelialization of cutaneous and oral wounds

Chernyavsky

Kalantari-Dehaghi

Phillips

et al. 2011

Wound Repair Regeneration

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It is well established that auto/paracrine acetylcholine (ACh) is essential for wound epithelialization, and that the mechanisms include regulation of keratinocyte motility and adhesion via nicotinic ACh receptors (nAChRs). Keratinocyte nAChRs can be also activated by non-canonical ligands, such as secreted mammalian Ly-6/urokinase-type plasminogen activator receptor-related protein (SLURP)-1 and -2. In this study, we determined effects of recombinant (r)SLURP-1 and-2 on migration of human epidermal and oral keratinocytes under agarose and epithelialization of cutaneous and mucosal excisional wounds in mice, and also identified nAChRs mediating SLURP signals. Both in vitro and in vivo, rSLURP-1 decreased and SLURP-2 increased epithelialization rate. The mixture of both peptides accelerated epithelialization even further, indicating that their simultaneous signaling renders an additive physiologic response. The specificity of rSLURP actions was illustrated by similar effects on cutaneous and oral wounds, which feature distinct responses to injury, and also by abrogation of rSLURP effects with neutralizing antibodies. rSLURP-1 acted predominantly via the α7 nAChR-coupled upregulation of the sedentary integrins α2 and α3, whereas SLURP-2—through α3, and α9 nAChRs upregulating migratory integrins α5 and αV. The biologic effects of rSLURPs required the presence of endogenous ACh, indicating that auto/paracrine SLURPs provide for a fine tuning of the physiologic regulation of crawling locomotion via the keratinocyte ACh axis. Since nAChRs have been shown to regulate SLURP production, cholinergic regulation of keratinocyte migration appears to be mediated by a reciprocally arranged network. The cholinergic peptides, therefore, may become prototype drugs for the treatment of wounds that fail to heal.

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Cited by 6 publications

References 34 publications

Circulating Brain Microvascular Endothelial Cells (cBMECs) as Potential Biomarkers of the Blood–Brain Barrier Disorders Caused by Microbial and Non-Microbial Factors

Circulating Brain Microvascular Endothelial Cells (cBMECs) as Potential Biomarkers of the Blood–Brain Barrier Disorders Caused by Microbial and Non-Microbial Factors

Molecular mechanisms of synergy of corneal muscarinic and nicotinic acetylcholine receptors in upregulation of E-cadherin expression

Novel cholinergic peptides SLURP‐1 and ‐2 regulate epithelialization of cutaneous and oral wounds

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