Romih R, Jezernik K, Masera A
Institute of Cell Biology, Medical Faculty, Ljubljana, Slovenia.
Histochem Cell Biol. 1998 Mar;109(3):263-9. doi: 10.1007/s004180050226.
A sodium saccharin (NaSac) diet was used to induce cell damage and regeneration in the urothelium of the male rat urinary bladder. Foci of terminally differentiated superficial cell exfoliation were detected after 5 weeks and their number increased after 10 and 15 weeks of the diet. At the sites of superficial cell loss, regenerative simple hyperplasia developed. Within 5 weeks of NaSac removal, regeneration re-established normal differentiated urothelium. In order to follow urothelial differentiation during regeneration we studied the expression of uroplakins and cytokeratins by means of immunocytochemistry and immunohistochemistry, respectively. Normal urothelium was characterised by terminally differentiated superficial cells which expressed uroplakins in their luminal plasma membrane and cytokeratin 20 (CK20) in the cytoplasm. Basal and intermediate cells were CK20 negative and cytokeratin 17 (CK17) positive. In hyperplastic urothelium all cells synthesised CK17, but not CK20. Differentiation of the superficial layer was reflected in three successive cell types: cells with microvilli, cells with rounded microridges and those with a rigid-looking plasma membrane on the luminal surface. The cells with microvilli did not stain with anti-uroplakin antibody. When the synthesis of uroplakins was detected rounded microridges were formed. With the elevated expression of uroplakins the luminal plasma membrane becomes rigid-looking which is characteristic of asymmetric unit membrane of terminally differentiated cells. During differentiation, synthesis of CK17 ceased in superficial cells while the synthesis of CK20 started. These results indicate that during urothelial regeneration after NaSac treatment, specific superficial cell types develop in which the switch to uroplakin synthesis and transition from CK17 to CK20 synthesis are crucial events for terminal differentiation.
用糖精钠（NaSac）饮食诱导雄性大鼠膀胱尿路上皮细胞损伤和再生。5周后检测到终末分化的表层细胞剥脱灶，饮食10周和15周后其数量增加。在表层细胞丢失部位，出现再生性单纯性增生。去除NaSac后5周内，再生重新建立了正常分化的尿路上皮。为了追踪再生过程中的尿路上皮分化，我们分别通过免疫细胞化学和免疫组织化学研究了uroplakins和细胞角蛋白的表达。正常尿路上皮的特征是终末分化的表层细胞，其在腔面膜中表达uroplakins，在细胞质中表达细胞角蛋白20（CK20）。基底细胞和中间细胞CK20阴性，细胞角蛋白17（CK17）阳性。在增生性尿路上皮中，所有细胞均合成CK17，但不合成CK20。表层的分化反映在三种连续的细胞类型中：具有微绒毛的细胞、具有圆形微嵴的细胞以及腔面具有看似刚性的质膜的细胞。具有微绒毛的细胞不被抗uroplakin抗体染色。当检测到uroplakins的合成时，形成圆形微嵴。随着uroplakins表达的升高，腔面膜变得看似刚性，这是终末分化细胞不对称单位膜的特征。在分化过程中，表层细胞中CK17的合成停止，而CK20的合成开始。这些结果表明，在NaSac处理后的尿路上皮再生过程中，特定的表层细胞类型发育，其中向uroplakin合成的转变以及从CKK17合成到CK20合成的转变是终末分化的关键事件。
