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Erschienen in: International Urology and Nephrology 8/2017

19.04.2017 | Urology – Original Paper

Involvement of interstitial cells of Cajal in bladder dysfunction in mice with experimental autoimmune encephalomyelitis

verfasst von: Zhibo Jin, Yinghui Ding, Rui Xue, Zhankui Jia, Zhenlin Huang, Yafei Ding, Chaohui Gu, Jinjian Yang

Erschienen in: International Urology and Nephrology | Ausgabe 8/2017

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Abstract

Background

Bladder dysfunction is an important symptom of experimental autoimmune encephalomyelitis (EAE). Our previous study showed that EAE-induced upregulation of the E-prostanoid receptor 3 (EP3) and E-prostanoid receptor 4 (EP4) in the bladder was accompanied by bladder dysfunction. Although many other studies have evaluated the lower urinary tract symptoms in multiple sclerosis, the mechanism remains unclear.

Objectives

To investigate the effects of interstitial cells of Cajal (ICC) on bladder dysfunction in a novel neurogenic bladder model induced by experimental autoimmune encephalomyelitis.

Materials and methods

The EAE model was induced by a previously established method, and bladder functions in mice were evaluated. Bladders were harvested for the analysis of ICCs and the genes associated with bladder mechanosensation including pannexin 1 (Panx1) and Gja1 (encoding connexin43) by immunofluorescence and western blotting. The stem cell factor cytokine (SCF) was intraperitoneally injected at the beginning of EAE onset.

Results

EAE mice developed profound bladder dysfunction characterized by significant urine retention, increased micturition and decreased urine output per micturition. EAE induced a significant decrease in c-Kit expression and ICCs number. EAE also induced a significant increase in pannexin 1 and connexin43. SCF treatment could ameliorate all of these pathological changes.

Conclusions

ICCs and stem cell factor play an important role in EAE-induced bladder dysfunction, which may be used as therapeutic options in treating patients with multiple sclerosis-related bladder dysfunction.
Literatur
3.
Zurück zum Zitat Ciancio SJ, Mutchnik SE, Rivera VM et al (2001) Urodynamic pattern changes in multiple sclerosis. Urology 57:239–245CrossRefPubMed Ciancio SJ, Mutchnik SE, Rivera VM et al (2001) Urodynamic pattern changes in multiple sclerosis. Urology 57:239–245CrossRefPubMed
4.
Zurück zum Zitat Altuntas CZ, Daneshgari F, Liu G et al (2008) Bladder dysfunction in mice with experimental autoimmune encephalomyelitis. J Neuroimmunol 203:58–63CrossRefPubMedPubMedCentral Altuntas CZ, Daneshgari F, Liu G et al (2008) Bladder dysfunction in mice with experimental autoimmune encephalomyelitis. J Neuroimmunol 203:58–63CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Altuntas CZ, Altuntas CZ, Daneshgari F et al (2012) Connective tissue and its growth factor CTGF distinguish the morphometric and molecular remodeling of the bladder in a model of neurogenic bladder. Am J Physiol Renal Physiol 303:1363–1369CrossRef Altuntas CZ, Altuntas CZ, Daneshgari F et al (2012) Connective tissue and its growth factor CTGF distinguish the morphometric and molecular remodeling of the bladder in a model of neurogenic bladder. Am J Physiol Renal Physiol 303:1363–1369CrossRef
6.
Zurück zum Zitat Vignes JR, Deloire MS, Petry KG et al (2007) Characterization and restoration of altered inhibitory and excitatory control of micturition reflex in experimental autoimmune encephalomyelitis in rats. J Physiol 578:439–450CrossRefPubMed Vignes JR, Deloire MS, Petry KG et al (2007) Characterization and restoration of altered inhibitory and excitatory control of micturition reflex in experimental autoimmune encephalomyelitis in rats. J Physiol 578:439–450CrossRefPubMed
7.
Zurück zum Zitat Fintl C, Hudson NP, Mayhew IG et al (2004) Interstitial cells of Cajal (ICC) in equine colic: an immunohistochemical study of horses with obstructive disorders of the small and large intestines. Equine Vet J 36:474–479CrossRefPubMed Fintl C, Hudson NP, Mayhew IG et al (2004) Interstitial cells of Cajal (ICC) in equine colic: an immunohistochemical study of horses with obstructive disorders of the small and large intestines. Equine Vet J 36:474–479CrossRefPubMed
8.
Zurück zum Zitat McCloskey KD (2010) Interstitial cells in the urinary bladder—localization and function. Neurourol Urodyn 29:82–87CrossRefPubMed McCloskey KD (2010) Interstitial cells in the urinary bladder—localization and function. Neurourol Urodyn 29:82–87CrossRefPubMed
9.
Zurück zum Zitat Horvath VJ, Vittal H, Lorincz A et al (2006) Reduced stem cell factor links smooth myopathy and loss of interstitial cells of cajal in murine diabetic gastroparesis. Gastroenterology 130:759–770CrossRefPubMed Horvath VJ, Vittal H, Lorincz A et al (2006) Reduced stem cell factor links smooth myopathy and loss of interstitial cells of cajal in murine diabetic gastroparesis. Gastroenterology 130:759–770CrossRefPubMed
10.
Zurück zum Zitat Chen W, Jiang C, Jin X et al (2011) Roles of stem cell factor on loss of interstitial cells of Cajal in bladder of diabetic rats. Urology 78(1443):e1–e6 Chen W, Jiang C, Jin X et al (2011) Roles of stem cell factor on loss of interstitial cells of Cajal in bladder of diabetic rats. Urology 78(1443):e1–e6
12.
Zurück zum Zitat Negoro H, Kanematsu A, Doi M et al (2012) Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm. Nat Commun 3:809CrossRefPubMedPubMedCentral Negoro H, Kanematsu A, Doi M et al (2012) Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm. Nat Commun 3:809CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Hao CM, Breyer MD (2008) Physiological regulation of prostaglandins in the kidney. Annu Rev Physiol 70:357–377CrossRefPubMed Hao CM, Breyer MD (2008) Physiological regulation of prostaglandins in the kidney. Annu Rev Physiol 70:357–377CrossRefPubMed
14.
Zurück zum Zitat Negoro H, Kanematsu A, Matsuo M et al (2013) Development of diurnal micturition pattern in mice after weaning. J Urol 189:740–746CrossRefPubMed Negoro H, Kanematsu A, Matsuo M et al (2013) Development of diurnal micturition pattern in mice after weaning. J Urol 189:740–746CrossRefPubMed
15.
Zurück zum Zitat Andersson KE, Pehrson R (2003) CNS involvement in overactive bladder: pathophysiology and opportunities for pharmacological intervention. Drugs 63:2595–2611CrossRefPubMed Andersson KE, Pehrson R (2003) CNS involvement in overactive bladder: pathophysiology and opportunities for pharmacological intervention. Drugs 63:2595–2611CrossRefPubMed
16.
Zurück zum Zitat Franken J, Gevaert T, Uvin P et al (2016) Urodynamic changes in mice with experimental autoimmune encephalomyelitis correlate with neurological impairment. Neurourol Urodyn 35:450–456CrossRefPubMed Franken J, Gevaert T, Uvin P et al (2016) Urodynamic changes in mice with experimental autoimmune encephalomyelitis correlate with neurological impairment. Neurourol Urodyn 35:450–456CrossRefPubMed
17.
18.
Zurück zum Zitat Lin L, Xu LM, Zhang W et al (2010) Roles of stem cell factor on the depletion of interstitial cells of Cajal in the colon of diabetic mice. Am J Physiol Gastrointest Liver Physiol 298:G241–G247CrossRefPubMed Lin L, Xu LM, Zhang W et al (2010) Roles of stem cell factor on the depletion of interstitial cells of Cajal in the colon of diabetic mice. Am J Physiol Gastrointest Liver Physiol 298:G241–G247CrossRefPubMed
19.
Zurück zum Zitat McCloskey KD, Anderson UA, Davidson RA et al (2009) Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice. Br J Pharmacol 156:273–283CrossRefPubMedPubMedCentral McCloskey KD, Anderson UA, Davidson RA et al (2009) Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice. Br J Pharmacol 156:273–283CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Timoteo MA, Carneiro I, Silva I, Noronha-Matos JB et al (2014) ATP released via pannexin-1 hemichannels mediates bladder overactivity triggered by urothelial P2Y6 receptors. Biochem Pharmacol 87:371–379CrossRefPubMed Timoteo MA, Carneiro I, Silva I, Noronha-Matos JB et al (2014) ATP released via pannexin-1 hemichannels mediates bladder overactivity triggered by urothelial P2Y6 receptors. Biochem Pharmacol 87:371–379CrossRefPubMed
22.
Zurück zum Zitat Christ GJ, Day NS, Day M et al (2003) Increased connexin43-mediated intercellular communication in a rat model of bladder overactivity in vivo. Am J Physiol Regul Integr Comp Physiol 284:R1241–R1248CrossRefPubMed Christ GJ, Day NS, Day M et al (2003) Increased connexin43-mediated intercellular communication in a rat model of bladder overactivity in vivo. Am J Physiol Regul Integr Comp Physiol 284:R1241–R1248CrossRefPubMed
23.
Zurück zum Zitat Negoro H, Kanematsu A, Imamura M et al (2011) Regulation of connexin 43 by basic fibroblast growth factor in the bladder: transcriptional and behavioral implications. J Urol 185:2398–2404CrossRefPubMed Negoro H, Kanematsu A, Imamura M et al (2011) Regulation of connexin 43 by basic fibroblast growth factor in the bladder: transcriptional and behavioral implications. J Urol 185:2398–2404CrossRefPubMed
24.
Zurück zum Zitat Imamura M, Negoro H, Kanematsu A et al (2009) Basic fibroblast growth factor causes urinary bladder overactivity through gap junction generation in the smooth muscle. Am J Physiol Renal Physiol 297:F46–F54CrossRefPubMed Imamura M, Negoro H, Kanematsu A et al (2009) Basic fibroblast growth factor causes urinary bladder overactivity through gap junction generation in the smooth muscle. Am J Physiol Renal Physiol 297:F46–F54CrossRefPubMed
Metadaten
Titel
Involvement of interstitial cells of Cajal in bladder dysfunction in mice with experimental autoimmune encephalomyelitis
verfasst von
Zhibo Jin
Yinghui Ding
Rui Xue
Zhankui Jia
Zhenlin Huang
Yafei Ding
Chaohui Gu
Jinjian Yang
Publikationsdatum
19.04.2017
Verlag
Springer Netherlands
Erschienen in
International Urology and Nephrology / Ausgabe 8/2017
Print ISSN: 0301-1623
Elektronische ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-017-1597-8

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