Characterization of the early proliferative response of the rodent bladder to subtotal cystectomy: a unique model of mammalian organ regeneration.
Characterization of the early proliferative response of the rodent bladder to subtotal cystectomy: a unique model of mammalian organ regeneration.
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DOI：
10.1371/journal.pone.0047414
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Christ G
中科院分区：
文献类型：
--
作者：
Peyton CC;Burmeister D;Petersen B;Andersson KE;Christ G
甲状腺素小计（STC;手术切除约75%的大鼠膀胱）引起强烈的增殖反应，导致在8周内完全的结构和功能性膀胱再生。这些研究的目的是表征介导这种再生现象的早期细胞反应，这在哺乳动物器官系统中是独特的。对18只12周龄雌性Fischer F344大鼠进行STC。在STC后1、3、5和7天，在腹腔内注射溴脱氧尿苷（BrdU）后2小时收获膀胱。荧光BrdU标记定量内的尿路上皮，固有层（LP），固有肌层（MP）和浆膜的细胞。用荧光共标记的细胞角蛋白、波形蛋白或平滑肌肌动蛋白（SMA）确认细胞位置，以分别鉴定尿路上皮细胞、间质细胞和平滑肌细胞。免疫组化法检测Shh、Gli-1和BMP-4的表达。三只未手术的大鼠注射BrdU作为对照。在对照膀胱中，膀胱壁中少于1%的细胞被BrdU标记，但在STC后的所有时间点，该百分比显著增加了5-8倍。增殖反应的时空特征被定义为一个显着更高的百分比BrdU标记的细胞内的尿路上皮在1天比在MP和LP。STC后3天和5天的时间依赖性变化显示MP中的BrdU标记细胞显著少于LP或尿路刺激。到7天，BrdU标记细胞的百分比在尿路上皮、LP和MP中相似。STC还引起Shh、Gli-1和BMP-4的免疫染色增加。总之，功能性膀胱再生的早期阶段的特征在于增殖细胞群的位置的时间依赖性变化，以及几种进化上保守的发育信号蛋白的表达。本报告扩展了以前的观察，并进一步建立了啮齿动物膀胱作为一个很好的模型，研究哺乳动物器官再生的新方面。
Subtotal cystectomy (STC; surgical removal of ∼75% of the rat urinary bladder) elicits a robust proliferative response resulting in complete structural and functional bladder regeneration within 8-weeks. The goal of these studies was to characterize the early cellular response that mediates this regenerative phenomenon, which is unique among mammalian organ systems. STC was performed on eighteen 12-week-old female Fischer F344 rats. At 1, 3, 5 and 7-days post-STC, the bladder was harvested 2-hours after intraperitoneal injection of bromodeoxyuridine (BrdU). Fluorescent BrdU labeling was quantified in cells within the urothelium, lamina propria (LP), muscularis propria (MP) and serosa. Cell location was confirmed with fluorescently co-labeled cytokeratin, vimentin or smooth muscle actin (SMA), to identify urothelial, interstitial and smooth muscle cells, respectively. Expression of sonic hedgehog (Shh), Gli-1 and bone morphogenic factor-4 (BMP-4) were evaluated with immunochemistry. Three non-operated rats injected with BrdU served as controls. Less than 1% of cells in the bladder wall were labeled with BrdU in control bladders, but this percentage significantly increased by 5-8-fold at all time points post-STC. The spatiotemporal characteristics of the proliferative response were defined by a significantly higher percentage of BrdU-labeled cells within the urothelium at 1-day than in the MP and LP. A time-dependent shift at 3 and 5-days post-STC revealed significantly fewer BrdU-labeled cells in the MP than LP or urothelium. By 7-days the percentage of BrdU-labeled cells was similar among urothelium, LP and MP. STC also caused an increase in immunostaining for Shh, Gli-1 and BMP-4. In summary, the early stages of functional bladder regeneration are characterized by time-dependent changes in the location of the proliferating cell population, and expression of several evolutionarily conserved developmental signaling proteins. This report extends previous observations and further establishes the rodent bladder as an excellent model for studying novel aspects of mammalian organ regeneration.
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