Histamine Induces ATP Release from Human Subcutaneous Fibroblasts, via Pannexin-1 Hemichannels, Leading to Ca2+ Mobilization and Cell Proliferation

Changes in the regulation of connective tissue ATP-mediated mechano-transduction and remodeling may be an important link to the pathogenesis of chronic pain. It has been demonstrated that mast cell-derived histamine plays an important role in painful fibrotic diseases. Here we analyzed the involvement of ATP in the response of human subcutaneous fibroblasts to histamine. Acute histamine application caused a rise in intracellular Ca2+ ([Ca2+]i) and ATP release from human subcutaneous fibroblasts via H1 receptor activation. Histamine-induced [Ca2+]i rise was partially attenuated by apyrase, an enzyme that inactivates extracellular ATP, and by blocking P2 purinoceptors with pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt and reactive blue 2. [Ca2+]i accumulation caused by histamine was also reduced upon blocking pannexin-1 hemichannels with 10Panx, probenecid, or carbenoxolone but not when connexin hemichannels were inhibited with mefloquine or 2-octanol. Brefeldin A, an inhibitor of vesicular exocytosis, also did not block histamine-induced [Ca2+]i mobilization. Prolonged exposure of human subcutaneous fibroblast cultures to histamine favored cell growth and type I collagen synthesis via the activation of H1 receptor. This effect was mimicked by ATP and its metabolite, ADP, whereas the selective P2Y1 receptor antagonist, MRS2179, partially attenuated histamine-induced cell growth and type I collagen production. Expression of pannexin-1 and ADP-sensitive P2Y1 receptor on human subcutaneous fibroblasts was confirmed by immunofluorescence confocal microscopy and Western blot analysis. In conclusion, histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to [Ca2+]i mobilization and cell growth through the cooperation of H1 and P2 (probably P2Y1) receptors.

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Combining Sandblasting, Alkaline Etching, and Collagen Immobilization to Promote Cell Growth on Biomedical Titanium Implants

Polymers ◽

10.3390/polym13152550 ◽

2021 ◽

Vol 13 (15) ◽

pp. 2550

Author(s):

Chia-Fei Liu ◽

Kai-Chun Chang ◽

Ying-Sui Sun ◽

Diem Thuy Nguyen ◽

Her-Hsiung Huang

Keyword(s):

Cell Growth ◽

Type I Collagen ◽

Bone Cells ◽

Surface Characteristics ◽

Attenuated Total Reflection ◽

Titanium Implants ◽

Type I ◽

Alkaline Etching ◽

Marrow Mesenchymal Stem Cells ◽

Collagen Immobilization

Our objective in this study was to promote the growth of bone cells on biomedical titanium (Ti) implant surfaces via surface modification involving sandblasting, alkaline etching, and type I collagen immobilization using the natural cross-linker genipin. The resulting surface was characterized in terms topography, roughness, wettability, and functional groups, respectively using field emission scanning electron microscopy, 3D profilometry, and attenuated total reflection-Fourier transform infrared spectroscopy. We then evaluated the adhesion, proliferation, initial differentiation, and mineralization of human bone marrow mesenchymal stem cells (hMSCs). Results show that sandblasting treatment greatly enhanced surface roughness to promote cell adhesion and proliferation and that the immobilization of type I collagen using genipin enhanced initial cell differentiation as well as mineralization in the extracellular matrix of hMSCs. Interestingly, the nano/submicro-scale pore network and/or hydrophilic features on sandblasted rough Ti surfaces were insufficient to promote cell growth. However, the combination of all proposed surface treatments produced ideal surface characteristics suited to Ti implant applications.

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Toll-Like Receptor-Triggered Calcium Mobilization Protects Mice against Bacterial Infection through Extracellular ATP Release

Infection and Immunity ◽

10.1128/iai.02546-14 ◽

2014 ◽

Vol 82 (12) ◽

pp. 5076-5085 ◽

Cited By ~ 29

Author(s):

Hua Ren ◽

Yunfei Teng ◽

Binghe Tan ◽

Xiaoyu Zhang ◽

Wei Jiang ◽

...

Keyword(s):

Immune Responses ◽

Pyridoxal Phosphate ◽

Atp Release ◽

Extracellular Atp ◽

Calcium Mobilization ◽

Innate Immune ◽

Disulfonic Acid ◽

Dependent Manner ◽

Innate Immune Responses ◽

Toll Like Receptor

ABSTRACTExtracellular ATP (eATP), released as a “danger signal” by injured or stressed cells, plays an important role in the regulation of immune responses, but the relationship between ATP release and innate immune responses is still uncertain. In this study, we demonstrated that ATP was released through Toll-like receptor (TLR)-associated signaling in bothEscherichia coli-infected mice and lipopolysaccharide (LPS)- or Pam3CSK4-treated macrophages. This ATP release could be blocked completely only byN-ethylmaleimide (NEM), not by carbenoxolone (CBX), flufenamic acid (FFA), or probenecid, suggesting the key role of exocytosis in this process. Furthermore, LPS-induced ATP release could also be reduced dramatically through suppressing calcium mobilization by use of U73122, caffeine, and thapsigargin (TG). In addition, the secretion of interleukin-1β (IL-1β) and CCL-2 was enhanced significantly by ATP, in a time- and dose-dependent manner. Meanwhile, macrophage-mediated phagocytosis of bacteria was also promoted significantly by ATP stimulation. Furthermore, extracellular ATP reduced the number of invading bacteria and protected mice from peritonitis by activating purinergic receptors. Mechanistically, phosphorylation of AKT and ERK was overtly increased by ATP in antibacterial immune responses. Accordingly, if we blocked the P2X- and P2Y-associated signaling pathway by using suramin and pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid), tetrasodium salt (PPADS), the ATP-enhanced immune response was restrained significantly. Taken together, our findings reveal an internal relationship between danger signals and TLR signaling in innate immune responses, which suggests a potential therapeutic significance of calcium mobilization-mediated ATP release in infectious diseases.

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Effect of exogenous ATP on canine jejunal smooth muscle

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2000.278.5.g725 ◽

2000 ◽

Vol 278 (5) ◽

pp. G725-G733 ◽

Cited By ~ 3

Author(s):

L. Xue ◽

G. Farrugia ◽

J. H. Szurszewski

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Pyridoxal Phosphate ◽

Electrical Field Stimulation ◽

Muscle Cells ◽

Disulfonic Acid ◽

Reactive Blue 2 ◽

Circular Smooth Muscle ◽

Inhibitory Junction Potential ◽

Junction Potential

Intracellular recordings were made from the circular smooth muscle cells of the canine jejunum to study the effect of exogenous ATP and to compare the ATP response to the nonadrenergic, noncholinergic (NANC) inhibitory junction potential (IJP) evoked by electrical field stimulation (EFS). Under NANC conditions, exogenous ATP evoked a transient hyperpolarization (6.5 ± 0.6 mV) and EFS evoked a NANC IJP (17 ± 0.4 mV). ω-Conotoxin GVIA (100 nM) and a low-Ca2+, high-Mg2+ solution abolished the NANC IJP but had no effect on the ATP-evoked hyperpolarization. The ATP-evoked hyperpolarization and the NANC IJP were abolished by apamin (1 μM) and N G-nitro-l-arginine (100 μM). Oxyhemoglobin (5 μM) partially (38.8 ± 5.5%) reduced the amplitude of the NANC IJP but had no effect on the ATP-evoked hyperpolarization. Neither the NANC IJP nor the ATP-evoked hyperpolarization was affected by P2 receptor antagonists or agonists, including suramin, reactive blue 2, 1-( N, O-bis-[5-isoquinolinesulfonyl]- N-methyl-l-tyrosyl)-4-phenylpiperazine, pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid, α,β-methylene ATP, 2-methylthioadenosine 5′-triphosphate tetrasodium salt, and adenosine 5′- O-2-thiodiphosphate. The data suggest that ATP evoked an apamin-sensitive hyperpolarization in circular smooth muscle cells of the canine jejunum via local production of NO in a postsynaptic target cell.

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Mechanical strain-induced Ca2+waves are propagated via ATP release and purinergic receptor activation

AJP Cell Physiology ◽

10.1152/ajpcell.2000.279.2.c295 ◽

2000 ◽

Vol 279 (2) ◽

pp. C295-C307 ◽

Cited By ~ 104

Author(s):

H. Sauer ◽

J. Hescheler ◽

M. Wartenberg

Keyword(s):

Gap Junctions ◽

Purinergic Receptor ◽

Mechanical Strain ◽

Atp Release ◽

Anion Channel ◽

Receptor Activation ◽

Disulfonic Acid ◽

Channel Blockers ◽

Junctional Coupling ◽

Intracellular Ca

Mechanical strain applied to prostate cancer cells induced an intracellular Ca2+ (Cai 2+) wave spreading with a velocity of 15 μm/s. Cai 2+ waves were not dependent on extracellular Ca2+ and membrane potential because propagation was unaffected in high-K+ and Ca2+-free solution. Waves did not depend on the cytoskeleton or gap junctions because cytochalasin B and nocodazole, which disrupt microfilaments and microtubules, respectively, and 1-heptanol, which uncouples gap junctions, were without effects. Fluorescence recovery after photobleaching experiments revealed an absence of gap junctional coupling. Cai 2+ waves were inhibited by the purinergic receptor antagonists basilen blue and suramin; by pretreatment with ATP, UTP, ADP, UDP, 2-methylthio-ATP, and benzoylbenzoyl-ATP; after depletion of ATP by 2-deoxyglucose; and after ATP scavenging by apyrase. Waves were abolished by the anion channel inhibitors 5-nitro-2-(3-phenylpropylamino)benzoic acid, tamoxifen, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid, niflumic acid, and gadolinium. ATP release following strain was significantly inhibited by anion channel blockers. Hence, ATP is secreted via mechanosensitive anion channels and activates purinergic receptors on the same cell or neighboring cells in an autocrine and paracrine manner, thus leading to Cai 2+ wave propagation.

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Modulation of Cell Growth and Matrix Metalloproteinase-2 Activation of Oral Squamous Cell Carcinoma as a Function of Culture Condition with Type I Collagen

Acta Oto-Laryngologica ◽

10.1080/00016480310016109 ◽

2003 ◽

Vol 123 (8) ◽

pp. 987-993 ◽

Cited By ~ 5

Author(s):

Hidenori Kinsenn ◽

Hiroshi Sato ◽

Mitsuru Furukawa ◽

Tomokazu Yoshizaki

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Growth ◽

Oral Squamous Cell Carcinoma ◽

Matrix Metalloproteinase ◽

Cell Carcinoma ◽

Squamous Cell ◽

Culture Condition ◽

Type I Collagen ◽

Matrix Metalloproteinase 2 ◽

Type I

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The Influence of Type I Collagen on the Development and Maintenance of the Osteoblast Phenotype in Primary and Passaged Rat Calvarial Osteoblasts: Modification of Expression of Genes Supporting Cell Growth, Adhesion, and Extracellular Matrix Mineralization

Experimental Cell Research ◽

10.1006/excr.1995.1005 ◽

1995 ◽

Vol 216 (1) ◽

pp. 35-45 ◽

Cited By ~ 269

Author(s):

Maureen P. Lynch ◽

Janet L. Stein ◽

Gary S. Stein ◽

Jane B. Lian

Keyword(s):

Extracellular Matrix ◽

Cell Growth ◽

Type I Collagen ◽

Supporting Cell ◽

Type I ◽

Matrix Mineralization ◽

Expression Of Genes

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Kynurenine Modulates MMP-1 and Type-I Collagen Expression Via Aryl Hydrocarbon Receptor Activation in Dermal Fibroblasts

Journal of Cellular Physiology ◽

10.1002/jcp.25383 ◽

2016 ◽

Vol 231 (12) ◽

pp. 2749-2760 ◽

Cited By ~ 17

Author(s):

Malihe-Sadat Poormasjedi-Meibod ◽

Sanam Salimi Elizei ◽

Victor Leung ◽

Reza Baradar Jalili ◽

Frank Ko ◽

...

Keyword(s):

Aryl Hydrocarbon Receptor ◽

Type I Collagen ◽

Receptor Activation ◽

Dermal Fibroblasts ◽

Type I ◽

Collagen Expression ◽

Aryl Hydrocarbon

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Activation of Na + /Ca 2+ Exchanger in Kinin B 1 Receptor-Stimulated Human Fibroblast Is Associated with Collagen Production

Hypertension ◽

10.1161/hyp.36.suppl_1.710 ◽

2000 ◽

Vol 36 (suppl_1) ◽

pp. 710-720

Author(s):

Jose R Romero ◽

Dennis A Ricupero ◽

Alicia Rivera ◽

Ronald H Goldstein ◽

Paul R Conlin

Keyword(s):

Connective Tissue ◽

Type I Collagen ◽

Fold Increase ◽

Receptor Activation ◽

Tissue Growth ◽

Northern Analysis ◽

Type I ◽

Mrna Levels ◽

Paracrine Factors ◽

Collagen Formation

P148 The arterial wall in hypertension is characterized by thickening of the media, in part due to increased deposition of connective tissue. Autocrine and paracrine factors may participate in this process; including products of the kallikrein-kinin system. We evaluated early signal transduction events and effects on collagen formation in B 1 -stimulated human myofibroblast cells (IMR-90). We measured cytosolic calcium (Ca cyt ) levels in cells loaded with FURA-2AM. Gene expression of connective tissue growth factor (CTGF) and α1(I) collagen was determined by estimating mRNA levels using Northern analysis of B 1 stimulated cells. Activation of the B 1 receptor with des-arg 10 -kallidin stimulated a three-fold increase in CTGF mRNA by increasing its stability. Furthermore, B 1 receptor activation caused an increase in α1(I) collagen mRNA and a four-fold increase in type I collagen synthesis in these cells; events not observed in B 2 receptor-stimulated cells. Activation of the B 1 receptor stimulated a dose dependent rise in Ca cyt (EC 50 =1.9nM) which was completely inhibited by des-arg 10 -[leu 9 ]-kallidin (100nM), a B 1 receptor antagonist. Isosmotic replacement of extracellular Na + with N -methyl,D-glucamine blocked > 90% of the B 1 stimulated rise in Ca cyt . A similar effect was observed when Ca 2+ was removed from the extracellular media, suggesting a role for the plasma membrane Na + /Ca 2+ exchanger (NCX). To further define a role for the NCX on CTGF formation we used dichlorobenzamil (DCB) and KB-R7943, two specific NCX inhibitors. DCB completely blocked the activation of B 1 receptor induced increase in CTGF mRNA stability while not affecting basal CTGF mRNA levels. In contrast, preincubation with EIPA, an amiloride analog, did not affect basal or stimulated CTGF mRNA levels. Furthermore, 60μM KB-R7943 blocked the B 1 stimulated rise in Ca cyt . NCX isoform 1 was identified in these cells using RT-PCR and immuno-detection. Thus, B 1 receptor stimulation increases fibrogenesis through a mechanism that involves modulation of cation metabolism via reverse-mode activation of NCX.

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P2Y2 receptors mediate ATP-induced resensitization of TRPV1 expressed by kidney projecting sensory neurons

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00235.2009 ◽

2010 ◽

Vol 298 (6) ◽

pp. R1634-R1641 ◽

Cited By ~ 12

Author(s):

Hui Wang ◽

Donna H. Wang ◽

James J. Galligan

Keyword(s):

Sensory Neurons ◽

Receptor Agonist ◽

Pyridoxal Phosphate ◽

Transient Receptor Potential ◽

Receptor Potential ◽

P2y Receptors ◽

Receptor Activation ◽

Sensory Nerves ◽

Disulfonic Acid ◽

Transient Receptor Potential Vanilloid

The transient receptor potential vanilloid type 1 (TRPV1) channel is a ligand-gated cation channel expressed by sensory nerves. P2Y receptors are G protein-coupled receptors that are also expressed by TRPV1-positive sensory neurons. Therefore, we studied interactions between P2Y receptors and TRPV1 function on kidney projecting sensory neurons. Application of Fast Blue (FB) to nerves surrounding the renal artery retrogradely labeled neurons in dorsal root ganglia of rats. Whole cell recording was performed on FB-labeled neurons maintained in primary culture. Capsaicin was used to activate TRPV1. Four types of kidney projecting neurons were identified based on capsaicin responses: 1) desensitizing (35%), 2) nondesensitizing (29%), 3) silent (3%), and 4) insensitive (30%). Silent neurons responded to capsaicin only after ATP (100 μM) pretreatment. ATP reversed desensitization in desensitizing neurons. Insensitive neurons never responded to capsaicin. UTP, a P2Y purinoceptor 2 (P2Y2)/P2Y4 receptor agonist, reversed capsaicin-induced TRPV1 desensitization. 2-methyl-thio-ATP (2-Me-S-ATP), a P2Y1 receptor agonist, did not change desensitization. MRS 2179 and pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), drugs that block P2Y1 receptors, did not block ATP-induced resensitization of TRPV1. Suramin, a P2Y2 receptor antagonist, blocked resensitization caused by UTP. Immunocytochemical studies showed that FB-labeled neurons coexpressed P2Y2 receptors and TRPV1. We conclude that P2Y2 receptor activation can maintain TRPV1 function perhaps during sustained episodes of activity of kidney projecting sensory neurons.

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