The hyaluronic acid receptor is induced by stretch injury of rat bladder in vivo and influences smooth muscle cell contraction in vitro
The hyaluronic acid receptor is induced by stretch injury of rat bladder in vivo and influences smooth muscle cell contraction in vitro
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DOI：
10.1097/00005392-199909010-00071
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发表时间：
1999-09-01
影响因子：
6.6
通讯作者：
McCulloch, L
中科院分区：
文献类型：
--
作者：
Bägli, DJ;Joyner, BD;McCulloch, L
目的：膀胱过度收缩和纤维化导致的膀胱顺应性丧失可能是膀胱内压力过大造成的损伤反应。细胞和细胞外基质成分之间的相互作用共同调节细胞对损伤和细胞外基质重塑的反应。透明质酸介导运动（RHAMM）受体是最近发现的一种透明质酸结合蛋白，已知在发育、损伤和癌症中影响多种类型的细胞胞外基质相互作用。我们评估了RHAMM在膀胱拉伸损伤早期事件中的作用。材料与方法：采用急性拉伸损伤模型。大鼠膀胱因水胀引起肉眼血尿损伤。采用免疫染色、western和逆转录聚合酶链式反应分析组织中RHAMM在粘膜和逼尿肌区域的时空表达。在已知阻断RHAMM功能的肽片段存在的情况下，使用凝胶收缩试验分析平滑肌细胞原代培养物的收缩活性。结果：急性腹水膨胀对膀胱造成直接、明显的损伤，平滑肌细胞束断裂，水肿出血。RHAMM在损伤后2小时内免疫定位于粘膜和逼尿肌，在5 ~ 10小时达到高峰。从低分子量（55 kD.）到高分子量（120 kD.）受体亚型的转变在免疫定位记录的表达高峰期间是显著的。损伤后5小时，RHAMM信使核糖核酸仅略有增加（40%）。在体外，平滑肌细胞原代培养积极启动并维持胶原凝胶的收缩，收缩幅度超过基线的75%。阻断RHAMM功能显著抑制了不到25%的平滑肌细胞在体外收缩凝胶的能力。结论：RHAMM表达增加是膀胱拉伸损伤引起的早期事件。由于细胞外基质透明质酸在组织修复反应的早期被发现，其受体RHAMM可能介导了膀胱对拉伸损伤的初始反应，其中一些反应（收缩）可能在体外实验中被阻断。由于该受体直接调节蛋白激酶信号传导，进而介导平滑肌细胞收缩和胶原合成，因此有必要进一步研究RHAMM在膀胱病理中的功能。
Purpose: Loss of bladder compliance from hypercontractility and fibrosis may represent an injury response to excessive intravesical pressure. Together, interactions between cell and extracellular matrix components regulate cell response to injury and extracellular matrix remodeling. The receptor for hyaluronic acid mediated motility (RHAMM) is a recently described hyaluronic acid binding protein known to influence multiple types of cell extracellular matrix interaction in development, injury and cancer. We evaluate the role of RHAMM in mediating early events in bladder stretch injury.Materials and Methods: An acute stretch injury model was used. The rat bladder was injured by hydrodistention inducing gross hematuria. Tissues were analyzed for temporal and spatial expression of RHAMM in the mucosa and detrusor regions by immunostaining, western and reverse transcriptase polymerase chain reaction analyses. The contractile activity of smooth muscle cell primary cultures was analyzed using a gel contraction assay in the presence of peptide fragments known to block RHAMM function.Results: Acute hydrodistention caused immediate and significant injury to the bladder, with fracturing of smooth muscle cell bundles, edema and hemorrhage. RHAMM immunolocalized to the mucosa and detrusor within 2 hours of injury, peaking by 5 to 10 hours. A shift from low molecular weight (55 kD.) to high (120 kD.) receptor isoforms was prominent during the peak expression period noted by immunolocalization. RHAMM messenger ribonucleic acid increased only slightly (40%) by 5 hours after injury. Smooth muscle cell primary cultures actively initiated and maintained the contraction of collagen gels by more than 75% of baseline in vitro. Blocking RHAMM function significantly inhibited the ability to less than 25% of smooth muscle cells to contract the gels in vitro.Conclusions: Increased expression of RHAMM is an early event precipitated by stretch injury to the bladder. Since extracellular matrix hyaluronic acid is found early in tissue repair responses, its receptor RHAMM may be mediating initial bladder responses to stretch injury, some of which (contraction) may be experimentally blocked in vitro. Since the receptor directly regulates protein kinase signaling which in turn mediates smooth muscle cell contraction and collagen synthesis, further studies of RHAMM function in bladder pathology are warranted.