Pampinella F, Roelofs M, Castellucci E, Passerini-Glazel G, Pagano F, Sartore S
Department of Biomedical Sciences, University of Padova, Italy.
J Urol. 1997 Feb;157(2):677-82.
We asked whether a urethral constriction gradually developed during growth would give rise to a structural remodeling of the bladder wall distinct from that of the mature rabbits in terms of cellular response.
We examined the serosa and detrusor muscle in immature rabbits whose urethra was obstructed at 30 days postnatal and studied 7 to 30 days after partial outlet obstruction. Morphometry, bromo-deoxyuridine (BrdU) incorporation, Western blotting and immunocytochemical staining with a panel of monoclonal antibodies specific to selected cytoskeletal, cytocontractile and membrane-related proteins unique to non-muscle and smooth muscle cells (SMC) were used to analyze the effects of obstruction on the differentiation pattern.
In comparison with results in adult obstructed bladders, we have found that in growing rabbits: (1) the cell conversion from fibroblasts to SMC, occurring within the 'extrinsic' region of serosal thickening, takes place earlier; (2) newly formed SMC are localized exclusively to the thickened serosa, and can group in bundles depending on the density of the regional innervation; (3) the peak level of BrdU incorporation is more elevated than in the adult bladder wall; and (4) change in the phenotypic profile of SMC of detrusor muscle is delayed.
These data indicate that the basic features of structural remodeling in the two models are similar, though partial outlet obstruction produced in growing animals accelerates the fibroblast conversion to SMC and their spatial, differentiation-specific arrangement in the serosa. The late phenotypic changes in obstructed detrusor muscle correlate with the decline of the DNA synthesis level after an initial burst and strongly suggest that newly formed SMC in the serosa do not derive from pre-existing SMC.
我们探讨了在生长过程中逐渐形成的尿道狭窄是否会导致膀胱壁结构重塑，在细胞反应方面与成年兔不同。
我们检查了出生后30天尿道被阻塞的未成熟兔的浆膜和逼尿肌，并在部分出口梗阻后7至30天进行研究。采用形态计量学、溴脱氧尿苷（BrdU）掺入、蛋白质免疫印迹以及用一组针对非肌肉和平滑肌细胞（SMC）特有的选定细胞骨架、细胞收缩和膜相关蛋白的单克隆抗体进行免疫细胞化学染色，以分析梗阻对分化模式的影响。
与成年梗阻膀胱的结果相比，我们发现在生长中的兔中：（1）成纤维细胞向SMC的细胞转化，发生在浆膜增厚的“外在”区域内，发生得更早；（2）新形成的SMC仅局限于增厚的浆膜，并且可以根据区域神经支配的密度成束聚集；（3）BrdU掺入的峰值水平比成年膀胱壁更高；（4）逼尿肌SMC表型特征的变化延迟。
这些数据表明，两种模型中结构重塑的基本特征相似，尽管在生长动物中产生的部分出口梗阻加速了成纤维细胞向SMC的转化及其在浆膜中的空间、分化特异性排列。梗阻性逼尿肌的晚期表型变化与初始爆发后DNA合成水平的下降相关，并强烈表明浆膜中新形成的SMC并非源自预先存在的SMC。
