Increased Expression of Neuregulin 1 and erbB2 Tyrosine Kinase in the Bladder of Rats With Cyclophosphamide-Induced Interstitial Cystitis
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: The aim of this study was to evaluate changes in expressions of neuregulin (NRG)1 and erbB2 tyrosine kinase (ErbB2) in bladders of rats with cyclophosphamide (CYP)-induced interstitial cystitis (IC). Methods: Twenty-four Sprague-Dawley rats were divided into the IC group (n=16) and the control group (n=8). After inducing IC with intraperitoneal CYP injection, expressions of NRG1 and ErbB2 were analyzed using western blotting and reverse transcriptase-polymerase chain reaction. Results: In Western blotting, relative intensities and distributions of both NRG1 and ErbB2 were approximately 1.5- and 3.2- fold higher, respectively, in the IC group than in the control group (mean±standard deviation: 1.42±0.09 vs. 0.93±0.15 and 0.93±0.16 vs. 0.29±0.08, P<0.05). In the rat bladder samples, mRNA expression levels of NRG1 and ErbB2 were higher in the IC group than in the control group (P<0.05). Conclusions: Our study has demonstrated significant changes in mRNA expression and immunoreactivity of NRG1 and ErbB2 receptors in the urinary bladder after CYP-induced IC. These results suggest that the up-regulated NRG1 may play a role in inducing an overactive bladder and promoting regeneration in the inflammatory bladder with CYP-induced IC.
Abstract
Purpose: The aim of this study was to evaluate changes in expressions of neuregulin (NRG)1 and erbB2 tyrosine kinase (ErbB2) in bladders of rats with cyclophosphamide (CYP)-induced interstitial cystitis (IC). Methods: Twenty-four Sprague-Dawley rats were divided into the IC group (n=16) and the control group (n=8). After inducing IC with intraperitoneal CYP injection, expressions of NRG1 and ErbB2 were analyzed using western blotting and reverse transcriptase-polymerase chain reaction. Results: In Western blotting, relative intensities and distributions of both NRG1 and ErbB2 were approximately 1.5- and 3.2- fold higher, respectively, in the IC group than in the control group (mean±standard deviation: 1.42±0.09 vs. 0.93±0.15 and 0.93±0.16 vs. 0.29±0.08, P<0.05). In the rat bladder samples, mRNA expression levels of NRG1 and ErbB2 were higher in the IC group than in the control group (P<0.05). Conclusions: Our study has demonstrated significant changes in mRNA expression and immunoreactivity of NRG1 and ErbB2 receptors in the urinary bladder after CYP-induced IC. These results suggest that the up-regulated NRG1 may play a role in inducing an overactive bladder and promoting regeneration in the inflammatory bladder with CYP-induced IC.
참고문헌 (27)
- Hanno PM, "American Urological Association. Diagnosis and treatment of interstitial cystitis", bladder pain syndrome: AUA guideline amendment, 2015, pp.193, 1545~1553
- 조군현, "Expression of Nitric Oxide Synthase and Aquaporin-3 in Cyclophosphamide Treated rat Bladder", International Neurourology Journal, 14(3), pp.149~156 (2010), 대한배뇨장애요실금학회
- Davis NF, "Interstitial cystitis", painful bladder syndrome: epidemiology, pathophysiology and evidence-based treatment options, 2014, pp.175, 30~37
- McMahon SB, "A model for the study of visceral pain states: chronic inflammation of the chronic decerebrate rat urinary bladder by irritant chemicals", Pain, 28, pp.109~127 (1987)
- Lantéri-Minet M, "Cyclophosphamide cystitis as a model of visceral pain in rats: model elaboration and spinal structures involved as revealed by the expression of c-Fos and Krox-24 proteins", Exp Brain Res, 105, pp.220~232 (1995)
- Nazif O, "Neural upregulation in interstitial cystitis", Urology, 69(4 Suppl), pp.24~33 (2007)
- Bade J, "Future research needs for the definition", diagnosis of interstitial cystitis, 2003, pp.(10Suppl), S31~S34
- Payne CK, "Research criteria versus clinical criteria for interstitial cystitis", Int J Urol, (10 Suppl), pp.S7~S10 (2003)
- Mei L, "Neuregulin 1 in neural development, synaptic plasticity and schizophrenia", Nat Rev Neurosci, 9, pp.437~452 (2008)
- Kim HG, "Neuregulin 1 up-regulates the expression of nicotinic acetylcholine receptors through the ErbB2", ErbB3-PI3K-MAPK signaling cascade in adult autonomic ganglion neurons, 2013, pp.124, 502~513
- Hanno P, "Status of international consensus on interstitial cystitis", bladder pain syndrome, Neurourol Urodyn, pp.2009, 28[DOI]
- Philip J, "Interstitial cystitis versus detrusor overactivity: a comparative, randomized, controlled study of cystometry using saline and 0.3 M potassium chloride", J Urol, 175, pp.566~570 (2006)
- Homma Y, "Clinical guidelines for interstitial cystitis and hypersensitive bladder syndrome", Int J Urol, 16, pp.597~615 (2009)
- Hedhli N, "Cardiovascular effects of neuregulin- 1", ErbB signaling: role in vascular signaling and angiogenesis, 2014, pp.20, 4899~4905
- Calvo M, "Neuregulin- ErbB signaling promotes microglial proliferation and chemotaxis contributing to microgliosis and pain after peripheral nerve injury", J Neurosci, 30, pp.5437~5450 (2010)
- Jiang YH, "Increased pro-inflammatory cytokines, C-reactive protein and nerve growth factor expressions in serum of patients with interstitial cystitis", bladder pain syndrome, 2013, pp.8, e76779~
- Dray A, "Inflammatory mediators of pain", Br J Anaesth, 75, pp.125~131 (1995)
- Cruz CD, "The ERK 1 and 2 pathway in the nervous system: from basic aspects to possible clinical applications in pain and visceral dysfunction", Curr Neuropharmacol, 5, pp.244~252 (2007)
- Imajo M, "Regulatory mechanisms and functions of MAP kinase signaling pathways", IUBMB Life, 58, pp.312~317 (2006)
- Yang SH, "MAP kinase signalling cascades and transcriptional regulation", Gene, 513, pp.1~13 (2013)
- Chan LK, "Tensin4 is up-regulated by EGF-induced ERK1", 2 activity and promotes cell proliferation and migration in hepatocellular carcinoma, 2015, pp.6, 20964~20976
- Dugan C, "Role of c-Jun Nterminal kinase (JNK) activation in micturition reflexes in cyclophosphamide (CYP)-induced cystitis in female rats", J Mol Neurosci, 54, pp.360~369 (2014)
- Jie P, "Activation of transient receptor potential vanilloid 4 induces apoptosis in hippocampus through downregulating PI3K", Akt and upregulating p38 MAPK signaling pathways, 2015, pp.6, e1775~
- Swiatkowski S, "Activities of MAP-kinase pathways in normal uroepithelial cells and urothelial carcinoma cell lines", Exp Cell Res, 282, pp.48~57 (2003)
- Corrow KA, "Phosphorylation of extracellular signalregulated kinases in urinary bladder in rats with cyclophosphamide- induced cystitis", Am J Physiol Regul Integr Comp Physiol, 293, pp.R125~R134 (2007)
- "Nrg1 is an injuryinduced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish"[URL]
- D’Uva G, "ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation", Nat Cell Biol, 17, pp.627~638 (2015)
