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膀胱出口部分梗阻时的平滑肌跨膜肌聚糖复合物

Smooth muscle trans-membrane sarcoglycan complex in partial bladder outlet obstruction.

作者信息

Macarak Edward J, Schulz Jake, Zderic Stephen A, Sado Yoshikazu, Ninomiya Yoshifumi, Polyak Erzsebet, Chacko Samuel, Howard Pamela S

机构信息

Department of Anatomy and Cell Biology School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104-6030, USA.

出版信息

Histochem Cell Biol. 2006 Jul;126(1):71-82. doi: 10.1007/s00418-005-0135-4. Epub 2006 Jan 25.

Abstract

The urinary bladder experiences both distension and contraction as a part of the normal filling and emptying cycle. To empty properly, tension generated intracellularly in a smooth muscle cell must be smoothly and efficiently transferred across its sarcolemma to the basement membrane, which mediates its binding to both the extracellular matrix and to other cells. As a consequence of urethral obstruction, the bladder cannot generate appropriate force to contract the organ, thereby leading to inefficient emptying and associated sequelae. In this study, an animal model of urethral obstruction was utilized to study the membrane-associated structures that transfer tension across the sarcolemma of bladder smooth muscle cells. Immunohistochemical localization of key components of the smooth muscle tension transfer apparatus (TTA) was performed utilizing specific antibodies against:(1) the alpha-chains of type IV collagen, a basement membrane component, and (2) beta-sarcoglycan, an integral membrane protein that is a participant in the physical linkage between the cytoskeleton and the basement membrane. We demonstrate, in obstructed animals, that there is a pronounced disruption of the TTA with a physical displacement of these two components that can be demonstrated at the level of the light microscope using scanning confocal microscopy. Electron microscopy further demonstrates significant increases in the size of the junctional plaques between smooth muscle cells.

摘要

膀胱在正常的充盈和排空周期中会经历扩张和收缩。为了正常排空,平滑肌细胞内产生的张力必须顺利且高效地穿过其肌膜传递到基底膜,基底膜介导其与细胞外基质和其他细胞的结合。由于尿道梗阻,膀胱无法产生适当的力量来收缩器官,从而导致排空效率低下及相关后遗症。在本研究中,利用尿道梗阻动物模型来研究跨膀胱平滑肌细胞肌膜传递张力的膜相关结构。利用针对以下物质的特异性抗体对平滑肌张力传递装置(TTA)的关键成分进行免疫组织化学定位:(1)IV型胶原的α链,一种基底膜成分;(2)β-肌聚糖,一种整合膜蛋白,参与细胞骨架与基底膜之间的物理连接。我们证明,在梗阻动物中,TTA存在明显破坏,这两种成分发生物理位移,使用扫描共聚焦显微镜在光学显微镜水平即可证实。电子显微镜进一步显示平滑肌细胞之间连接斑的大小显著增加。

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