Beyond neurons: Involvement of urothelial and glial cells in bladder function.
Beyond neurons: Involvement of urothelial and glial cells in bladder function.
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DOI：
10.1002/nau.20747
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发表时间：
2010
影响因子：
2
通讯作者：
Hanna-Mitchell, Ann T.
中科院分区：
文献类型：
--
作者：
Birder, Lori A.;Wolf-Johnston, Amanda S.;Chib, Manjul K.;Buffington, Charles A.;Roppolo, James R.;Hanna-Mitchell, Ann T.
尿路上皮或下尿路上皮衬里（LUT）可能通过与膀胱神经、平滑肌以及免疫和炎症系统的细胞积极沟通而在膀胱功能中发挥重要作用。最近的证据支持非神经元细胞的重要性，这些细胞可以延伸到神经元的外周和中枢突起，这些神经元从膀胱传递正常和伤害性信号。使用被诊断患有自然发生的综合征（称为猫间质性膀胱炎（FIC））的猫，我们研究了与膀胱中感觉转导相关的3种细胞类型内是否发生生理参数的变化：1）尿路上皮，2）经鉴定的膀胱背根神经节（DRG）神经元和3）腰骶（S1）脊髓中的灰质星形胶质细胞。由于雌激素波动可能调节许多慢性盆腔疼痛综合征的严重程度，我们还研究了17β-雌二醇（E2）是否改变大鼠尿路上皮细胞的细胞信号转导。我们已经确定了增加神经生长因子（NGF）和P物质（SP）在尿路上皮从FIC猫在尿路上皮从未受影响的（对照）膀胱。本研究报道，FIC尿刺激引起的NGF表达升高可能是FIC猫DRG神经元胞体大小增加的原因。在脊髓水平，星形胶质细胞GFAP免疫强度显着升高，并且有证据表明FIC S1脊髓区域（浅背角和深背角、中央管和V-VII层）中原始中间丝、巢蛋白（均指示反应状态）共表达，这些区域接收来自盆腔传入神经的输入。最后，我们发现，E2触发了大鼠尿路上皮细胞中的p38 MAPK的发情修饰激活。在动情间期和动情期，E2介导的p38 MAPK升高，动情前期的p38 MAPK抑制，存在周期性变化。虽然尿路上皮细胞通常被视为内脏感觉处理的旁观者，但这些和其他研究结果支持这些细胞作为某些物理和化学刺激的主要换能器的观点。此外，脊髓星形胶质细胞在膀胱疼痛综合征（BPS）的动物模型中的显著激活可能在疼痛综合征中起重要作用，并为药物干预开辟了新的潜在途径。
The urothelium, or epithelial lining of the lower urinary tract (LUT), is likely to play an important role in bladder function by actively communicating with bladder nerves, smooth muscle, and cells of the immune and inflammatory systems. Recent evidence supports the importance of non-neuronal cells that may extend to both the peripheral and central processes of the neurons that transmit normal and nociceptive signals from the urinary bladder. Using cats diagnosed with a naturally occurring syndrome termed feline interstitial cystitis (FIC), we investigated whether changes in physiologic parameters occur within 3 cell types associated with sensory transduction in the urinary bladder: 1) the urothelium, 2) identified bladder dorsal root ganglion (DRG) neurons and 3) grey matter astrocytes in the lumbosacral (S1) spinal cord. As estrogen fluctuations may modulate the severity of many chronic pelvic pain syndromes, we also examined whether 17β-estradiol (E2) alters cell signaling in rat urothelial cells. We have identified an increase in nerve growth factor (NGF) and substance P (SP) in urothelium from FIC cats over that seen in urothelium from unaffected (control) bladders. The elevated NGF expression by FIC urothelium is a possible cause for the increased cell body size of DRG neurons from cats with FIC, reported in this study. At the level of the spinal cord, astrocytic GFAP immuno-intensity was significantly elevated and there was evidence for co-expression of the primitive intermediate filament, nestin (both indicative of a reactive state) in regions of the FIC S1 cord (superficial and deep dorsal horn, central canal and laminae V-VIl) that receive input from pelvic afferents. Finally, we find that E2 triggers an estrus-modifiable activation of p38 MAPK in rat urothelial cells. There were cyclic variations with E2-mediated elevation of p38 MAPK at both diestrus and estrus, and inhibition of p38 MAPK in proestrous urothelial cells. Though urothelial cells are often viewed as bystanders in the processing of visceral sensation, these and other findings support the view that these cells function as primary transducers of some physical and chemical stimuli. In addition, the pronounced activation of spinal cord astrocytes in an animal model for bladder pain syndrome (BPS) may play an important role in the pain syndrome and open up new potential approaches for drug intervention.
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DOI：
10.1152/ajprenal.00098.2005
发表时间：
2006-01-01
影响因子：
4.2
作者：
Beckel, JM;Kanai, A;Birder, LA
通讯作者：
Birder, LA
影响因子：
64.8
作者：
Chang, LF;Karin, M
通讯作者：
Karin, M
影响因子：
3.3
作者：
Balestreire, Elena M.;Apodaca, Gerard
通讯作者：
Apodaca, Gerard
影响因子：
1.7
作者：
Buffington, C. A. Tony;Westropp, Jodi L.;Bolus, Roger R.
通讯作者：
Bolus, Roger R.
DOI：
10.1152/ajprenal.00056.2003
发表时间：
2003-09-01
影响因子：
4.2
作者：
Birder, LA;Barrick, SR;Buffington, CA
通讯作者：
Buffington, CA