scholarly journals Expression and function of CXCL12/CXCR4 in rat urinary bladder with cyclophosphamide-induced cystitis

2010 ◽  
Vol 298 (3) ◽  
pp. F589-F600 ◽  
Author(s):  
Lauren Arms ◽  
Beatrice M. Girard ◽  
Margaret A. Vizzard
Keyword(s):  
Urinary Bladder ◽  
Tissue Injury ◽  
Bladder Capacity ◽  
Rat Urinary Bladder ◽  
Cxcr4 Signaling ◽  
Qrt Pcr ◽  
Proinflammatory Mediators ◽  
Bladder Inflammation ◽  
And Function

Chemokines, otherwise known as chemotactic cytokines, are proinflammatory mediators of the immune response and have been implicated in altered sensory processing, hyperalgesia, and central sensitization following tissue injury or inflammation. To address the role of CXCL12/CXCR4 signaling in normal micturition and inflammation-induced bladder hyperreflexia, bladder inflammation in adult female Wistar rats (175–250 g) was induced by injecting cyclophosphamide (CYP) intraperitoneally at acute (150 mg/kg; 4 h), intermediate (150 mg/kg; 48 h), and chronic (75 mg/kg; every 3rd day for 10 days) time points. CXCL12, and its receptor, CXCR4, were examined in the whole urinary bladder of control and CYP-treated rats using enzyme-linked immunosorbent assays (ELISAs), quantitative PCR (qRT-PCR), and immunostaining techniques. ELISAs, qRT-PCR, and immunostaining experiments revealed a significant ( P ≤ 0.01) increase in CXCL12 and CXCR4 expression in the whole urinary bladder, and particularly in the urothelium, with CYP treatment. The functional role of CXCL12/CXCR4 signaling in micturition was evaluated using conscious cystometry with continuous instillation of saline and CXCR4 receptor antagonist (AMD-3100; 5 μM) administration in control and CYP (48 h)-treated rats. Receptor blockade of CXCR4 using AMD-3100 increased bladder capacity in control (no CYP) rats and reduced CYP-induced bladder hyperexcitability as demonstrated by significant ( P ≤ 0.01) increases in intercontraction interval, bladder capacity, and void volume. These results suggest a role for CXCL12/CXCR4 signaling in both normal micturition and with bladder hyperreflexia following bladder inflammation.

scholarly journals Expression and function of CCL2/CCR2 in rat micturition reflexes and somatic sensitivity with urinary bladder inflammation

2013 ◽  
Vol 305 (1) ◽  
pp. F111-F122 ◽  
Author(s):  
Lauren Arms ◽  
Beatrice M. Girard ◽  
Susan E. Malley ◽  
Margaret A. Vizzard
Keyword(s):  
Urinary Bladder ◽  
Therapeutic Potential ◽  
Pain Syndrome ◽  
Bladder Capacity ◽  
Bladder Pain Syndrome ◽  
Bladder Pain ◽  
Monocyte Chemoattractant Protein 1 ◽  
Functional Roles ◽  
Proinflammatory Mediators ◽  
Bladder Inflammation

Chemokines are proinflammatory mediators of the immune response, and there is growing evidence for chemokine/receptor signaling involvement in pronociception. Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder-related with at least one urinary symptom. We have explored the expression and functional roles of CCL2 (monocyte chemoattractant protein-1) and its high-affinity receptor, CCR2, in micturition reflex function and somatic sensitivity in rats with urinary bladder inflammation induced by cyclophosphamide (CYP) treatment of varying duration (4 h, 48 h, chronic). Real-time quantitative RT-PCR, ELISAs, and immunohistochemistry demonstrated significant ( P ≤ 0.01) increases in CCL2 and CCR2 expression in the urothelium and in Fast Blue-labeled bladder afferent neurons in lumbosacral dorsal root ganglia with CYP-induced cystitis. Intravesical infusion of RS504393 (5 μM), a specific CCR2 antagonist, reduced voiding frequency and increased bladder capacity and void volume in rats with CYP-induced cystitis (4 h), as determined with open outlet, conscious cystometry. In addition, CCR2 blockade, at the level of the urinary bladder, reduced referred somatic sensitivity of the hindpaw and pelvic region in rats with CYP treatment, as determined with von Frey filament testing. We provide evidence of functional roles for CCL2/CCR2 signaling at the level of the urinary bladder in reducing voiding frequency and somatic sensitivity following CYP-induced cystitis (4 h). These studies suggest that chemokines/receptors may be novel targets with therapeutic potential in the context of urinary bladder inflammation.

scholarly journals Role for pAKT in rat urinary bladder with cyclophosphamide (CYP)-induced cystitis

2011 ◽  
Vol 301 (2) ◽  
pp. F252-F262 ◽  
Author(s):  
Lauren Arms ◽  
Margaret A. Vizzard
Keyword(s):  
Urinary Bladder ◽  
Bladder Capacity ◽  
Intravesical Instillation ◽  
Bladder Function ◽  
Rat Urinary Bladder ◽  
Akt Phosphorylation ◽  
Somatic Pain ◽  
Time Points ◽  
Bladder Inflammation ◽  
Female Wistar Rats

AKT phosphorylation following peripheral nerve injury or inflammation may play a role in somatic pain processes and visceral inflammation. To examine such a role in micturition reflexes with bladder inflammation, we induced bladder inflammation in adult female Wistar rats (200–300 g) by injecting cyclophosphamide (CYP) intraperitoneally at acute (150 mg/kg; 4 h), intermediate (150 mg/kg; 48 h), and chronic (75 mg/kg; every third day for 10 days) time points. Western blot analyses of whole urinary bladders showed significant increases ( P ≤ 0.01) in phosphorylated (p) AKT at all time points; however, the magnitude of AKT phosphorylation varied with duration of CYP treatment. Immunohistochemical analyses of pAKT immunoreactivity (pAKT-IR) in cryostat bladder sections demonstrated duration-dependent, significant ( P ≤ 0.01) increases in pAKT-IR in both the urothelium and detrusor smooth muscle of CYP-inflamed bladders. Additionally, a suburothelial population of pAKT-IR macrophages (CD68-, MAC2-, and F4/80-positive) was present in chronic CYP-treated bladders. The functional role of pAKT in micturition was evaluated using open, conscious cystometry with continuous instillation of saline in conjunction with administration of an inhibitor of AKT phosphorylation, deguelin (1.0 μg/10 μl), or vehicle (1% DMSO in saline) in control (no inflammation) and CYP (48 h)-treated rats. Bladder capacity, void volume, and intercontraction void interval increased significantly ( P ≤ 0.05) following intravesical instillation of deguelin in CYP (48 h)-treated rats. These results demonstrate increased AKT phosphorylation in the urinary bladder with urinary bladder inflammation and that blockade of AKT phosphorylation in the urothelium improves overall bladder function.

THE ROLE OF INTERLEUKIN-6 ON THE CONTRACTILE RESPONSES OF RAT URINARY BLADDER

2006 ◽  
Vol 5 (2) ◽  
pp. 79
Author(s):  
S.C. Myung ◽  
M.Y. Lee ◽  
M.K. Lee ◽  
S.H. Ahn ◽  
T.H. Kim ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Interleukin 6 ◽  
Rat Urinary Bladder ◽  
Contractile Responses

scholarly journals Expression and functional role of Rho-kinase in rat urinary bladder smooth muscle

2003 ◽  
Vol 138 (5) ◽  
pp. 757-766 ◽  
Author(s):  
Alexandra Wibberley ◽  
Zunxuan Chen ◽  
Erding Hu ◽  
J Paul Hieble ◽  
Timothy D Westfall
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Functional Role ◽  
Rho Kinase ◽  
Bladder Smooth Muscle ◽  
Rat Urinary Bladder ◽  
Urinary Bladder Smooth Muscle

scholarly journals Chorionic Villous Mesenchymal Stem Cells Derived Exosomes Deliver miR-135b-5p to Trophoblasts, Promoting their Proliferation and Invasion by Targeting TXNIP via β-Catenin Pathway

2020 ◽  
Author(s):  
Yijing Chu ◽  
Yan Zhang ◽  
Guoqiang Gao ◽  
Jun Zhou ◽  
Yang Lv ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tissue Injury ◽  
Luciferase Reporter ◽  
Rna Seq ◽  
Qrt Pcr ◽  
Reporter Assays ◽  
Pcr Assays ◽  
Proliferation And Invasion

Abstract Background: Human chorionic villous mesenchymal stem cells (CV-MSCs) are found to be a promising and effective treatment for tissue injury. Trophoblast dysfunction during pregnancies is significantly involved in the pathogenesis of preeclampsia (PE). This work was to understand how CV-MSCs regulated trophoblast function. Methods: In this study, we treated trophoblasts with CV-MSC-derived exosomes and RNA-seq analysis was used to understand the changes in trophoblasts. We examined the levels of TXNIP and β-catenin in trophoblasts by immunohistochemistry, western blot and qRT-PCR assays. Luciferase reporter assays and qRT-PCR assays were used to understand the role of miR135b-5p in the effects of CV-MSC-derived exosomes. The growth and invasion of trophoblasts was evaluated with the CCK-8 and transwell assays. Results: The treatment markedly enhanced the trophoblast proliferation and invasion. Furthermore, a significant decrease of TXNIP expression and inactivation of the β-catenin pathway in CV-MSCs exosomes-treated trophoblasts was observed. Consistent with these findings, TXNIP inhibition exhibited the same effect of promoting trophoblast proliferation and invasion as induced by CV-MSC-derived exosomes, also with the accompaniment of inactivation of β-catenin pathway. In addition, overexpression of TXNIP activated the β-catenin pathway in trophoblasts, and reduced the proliferation and invasion of trophoblasts. Importantly, miR135b-5p was found to be highly expressed in CV-MSC exosomes and interact with TXNIP. The miR-135b-5p overexpression significantly elevated the proliferation and invasion of trophoblasts, which could be attenuated by TXNIP overexpression. Conclusion: Our results suggest that TXNIP-dependent β-catenin pathway inactivation mediated by miR135b-5p which is delivered by CV-MSC-derived exosomes could promote the proliferation and invasion of trophoblasts.

scholarly journals Expression and function of bradykinin B1 and B2 receptors in normal and inflamed rat urinary bladder urothelium

2005 ◽  
Vol 562 (3) ◽  
pp. 859-871 ◽  
Author(s):  
Bikramjit Chopra ◽  
Stacey R. Barrick ◽  
Susan Meyers ◽  
Jonathan M. Beckel ◽  
Mark L. Zeidel ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Rat Urinary Bladder ◽  
Bladder Urothelium ◽  
B2 Receptors ◽  
And Function

scholarly journals A possible role of the cholinergic and purinergic receptor interaction in the regulation of the rat urinary bladder function

2012 ◽  
Vol 32 (6) ◽  
pp. 421-431 ◽  
Author(s):  
Ágnes Jenes ◽  
Ferenc Ruzsnavszky ◽  
Andrea Telek ◽  
Gyula P. Szigeti ◽  
László Csernoch
Keyword(s):  
Urinary Bladder ◽  
Purinergic Receptor ◽  
Bladder Function ◽  
Receptor Interaction ◽  
Rat Urinary Bladder

The role of cholinesterases in rat urinary bladder contractility

2003 ◽  
Vol 31 (3) ◽  
pp. 223-226 ◽  
Author(s):  
Tsutomu Nakahara ◽  
Yuko Kubota ◽  
Kenji Sakamoto ◽  
Kunio Ishii
Keyword(s):  
Urinary Bladder ◽  
Rat Urinary Bladder

scholarly journals Role of p75NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

2008 ◽  
Vol 295 (6) ◽  
pp. F1778-F1789 ◽  
Author(s):  
Mary Beth Klinger ◽  
Margaret A. Vizzard
Keyword(s):  
Urinary Bladder ◽  
Intravesical Instillation ◽  
Bladder Function ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Female Rat ◽  
Rat Urinary Bladder ◽  
Micturition Reflex ◽  
Reflex Pathways

Previous studies demonstrated changes in urinary bladder neurotrophin content and upregulation of neurotrophin receptors, TrkA and the p75 neurotrophin receptor (p75NTR), in micturition reflex pathways after cyclophosphamide (CYP)-induced cystitis. p75NTR can bind nerve growth factor (NGF) and modulate NGF-TrkA binding and signaling. We examined p75NTR expression and the role of p75NTR in the micturition reflex in control and CYP-treated rats. p75NTR Immunoreactivity was present throughout the urinary bladder. CYP-induced cystitis (4 h, 48 h, chronic) increased ( P ≤ 0.05) p75NTR expression in whole urinary bladder as shown by Western blotting. The role of p75NTR in bladder function in control and CYP-treated rats was determined using conscious cystometry and immunoneutralization or PD90780, a compound known to specifically block NGF binding to p75NTR. An anti-p75NTR monoclonal antibody or PD90780 was infused intravesically and cystometric parameters were evaluated. Both methods of p75NTR blockade significantly ( P ≤ 0.05) decreased the intercontraction interval and void volume in control and CYP-treated rats. Intravesical infusion of PD90780 also significantly ( P ≤ 0.001) increased intravesical pressure and increased the number of nonvoiding contractions during the filling phase. Control intravesical infusions of isotype-matched IgG and vehicle were without effect. Intravesical instillation of PD90780 significantly ( P ≤ 0.01) reduced the volume threshold to elicit a micturition contraction in control rats (no inflammation) and CYP-treated in a closed urinary bladder system. These studies demonstrate 1) ubiquitous p75NTR expression in urinary bladder and increased expression with CYP-induced cystitis and 2) p75NTR blockade at the level of the urinary bladder produces bladder hyperreflexia in control and CYP-treated rats. The overall activity of the urinary bladder reflects the balance of NGF-p75NTR and NGF-TrkA signaling.

scholarly journals Stimulation of β3-adrenoceptors relaxes rat urinary bladder smooth muscle via activation of the large-conductance Ca2+-activated K+ channels

2008 ◽  
Vol 295 (5) ◽  
pp. C1344-C1353 ◽  
Author(s):  
Kiril L. Hristov ◽  
Xiangli Cui ◽  
Sean M. Brown ◽  
Lei Liu ◽  
Whitney F. Kellett ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Bk Channels ◽  
Bk Channel ◽  
Bladder Smooth Muscle ◽  
Rat Urinary Bladder ◽  
Urinary Bladder Smooth Muscle ◽  
Brl 37344 ◽  
Stimulation Of

We investigated the role of large-conductance Ca2+-activated K+ (BK) channels in β3-adrenoceptor (β3-AR)-induced relaxation in rat urinary bladder smooth muscle (UBSM). BRL 37344, a specific β3-AR agonist, inhibits spontaneous contractions of isolated UBSM strips. SR59230A, a specific β3-AR antagonist, and H89, a PKA inhibitor, reduced the inhibitory effect of BRL 37344. Iberiotoxin, a specific BK channel inhibitor, shifts the BRL 37344 concentration response curves for contraction amplitude, net muscle force, and tone to the right. Freshly dispersed UBSM cells and the perforated mode of the patch-clamp technique were used to determine further the role of β3-AR stimulation by BRL 37344 on BK channel activity. BRL 37344 increased spontaneous, transient, outward BK current (STOC) frequency by 46.0 ± 20.1%. In whole cell mode at a holding potential of Vh = 0 mV, the single BK channel amplitude was 5.17 ± 0.28 pA, whereas in the presence of BRL 37344, it was 5.55 ± 0.41 pA. The BK channel open probability was also unchanged. In the presence of ryanodine and nifedipine, the current-voltage relationship in response to depolarization steps in the presence and absence of BRL 37344 was identical. In current-clamp mode, BRL 37344 caused membrane potential hyperpolarization from −26.1 ± 2.1 mV (control) to −29.0 ± 2.2 mV. The BRL 37344-induced hyperpolarization was eliminated by application of iberiotoxin, tetraethylammonium or ryanodine. The data indicate that stimulation of β3-AR relaxes rat UBSM by increasing the BK channel STOC frequency, which causes membrane hyperpolarization and thus relaxation.

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