Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK.
J Cell Mol Med. 2012 Jul;16(7):1533-43. doi: 10.1111/j.1582-4934.2011.01410.x.
Changes in the distribution of interstitial cells (IC) are reportedly associated with dysfunctional bladder. This study investigated whether spinal cord injury (SCI) resulted in changes to IC subpopulations (vimentin-positive with the ultrastructural profile of IC), smooth muscle and nerves within the bladder wall and correlated cellular remodelling with functional properties. Bladders from SCI (T8/9 transection) and sham-operated rats 5 weeks post-injury were used for ex vivo pressure-volume experiments or processed for morphological analysis with transmission electron microscopy (TEM) and light/confocal microscopy. Pressure-volume relationships revealed low-pressure, hypercompliance in SCI bladders indicative of decompensation. Extensive networks of vimentin-positive IC were typical in sham lamina propria and detrusor but were markedly reduced post-SCI; semi-quantitative analysis showed significant reduction. Nerves labelled with anti-neurofilament and anti-vAChT were notably decreased post-SCI. TEM revealed lamina propria IC and detrusor IC which formed close synaptic-like contacts with vesicle-containing nerve varicosities in shams. Lamina propria and detrusor IC were ultrastructurally damaged post-SCI with retracted/lost cell processes and were adjacent to areas of cellular debris and neuronal degradation. Smooth muscle hypertrophy was common to SCI tissues. In conclusion, IC populations in bladder wall were decreased 5 weeks post-SCI, accompanied with reduced innervation, smooth muscle hypertrophy and increased compliance. These novel findings indicate that bladder wall remodelling post-SCI affects the integrity of interactions between smooth muscle, nerves and IC, with compromised IC populations. Correlation between IC reduction and a hypercompliant phenotype suggests that disruption to bladder IC contribute to pathophysiological processes underpinning the dysfunctional SCI bladder.
据报道，间质细胞（IC）分布的变化与功能失调的膀胱有关。本研究调查了脊髓损伤（SCI）是否导致膀胱壁内 IC 亚群（波形蛋白阳性，具有 IC 的超微结构特征）、平滑肌和神经的变化，并将细胞重塑与功能特性相关联。损伤后 5 周的 SCI（T8/9 横断）和假手术大鼠的膀胱用于离体压力-容积实验，或进行透射电镜（TEM）和光/共聚焦显微镜形态学分析。压力-容积关系显示 SCI 膀胱具有低压、高顺应性，表明代偿失调。广泛的波形蛋白阳性 IC 网络在假层状固有层和逼尿肌中很典型，但 SCI 后明显减少；半定量分析显示明显减少。用抗神经丝和抗 vAChT 标记的神经明显减少。TEM 显示，在 sham 中，固有层 IC 和逼尿肌 IC 与含有囊泡的神经末梢形成紧密的突触样接触；在 sham 中，固有层和逼尿肌 IC 超微结构受损，细胞突起回缩/丢失，并与细胞碎片和神经元降解相邻。平滑肌肥大在 SCI 组织中很常见。总之，SCI 后 5 周膀胱壁 IC 数量减少，伴随支配减少、平滑肌肥大和顺应性增加。这些新发现表明，SCI 后膀胱壁的细胞重塑影响平滑肌、神经和 IC 之间相互作用的完整性，导致 IC 群体受损。IC 减少与高顺应性表型之间的相关性表明，膀胱 IC 的破坏可能导致功能失调的 SCI 膀胱的病理生理过程。
