Baskin L, DiSandro M, Li Y, Li W, Hayward S, Cunha G
Department of Urology, University of California, San Francisco, California, USA.
J Urol. 2001 Apr;165(4):1283-8.
We have previously shown that mesenchymal-epithelial interactions are necessary for the development of bladder smooth muscle. Specifically without fetal or adult urothelium embryonic rat bladder mesenchyma does not differentiate into smooth muscle. The mechanism responsible for this interaction is not known, although it is postulated that diffusable growth factors have a role. Our hypothesis is that diffusable factors within adult rat bladders influence smooth muscle differentiation.
Chimeric bladders were created by surgically implanting 14-day embryonic rat bladder mesenchyma before smooth muscle differentiation into the detrusor space of adult syngeneic hosts to test whether the host urothelium would induce smooth muscle differentiation without being in direct contact with fetal bladder mesenchymal tissue. Sub-detrusor pockets were created between the serosa and smooth muscle layer, between the smooth muscle layer and lamina propria, and between the lamina propria and urothelium in direct contact with urothelium. Controls consisted of intact 14-day embryonic rat bladders with the urothelium not removed, and 14-day embryonic bladder mesenchyma recombined with urothelium (direct contact) placed within the sub-detrusor space of the bladder and under the renal capsule.
Immunohistochemical staining with antibodies directed against smooth muscle alpha-actin and urothelium (cytokeratin 7) revealed smooth muscle differentiation in intact embryonic bladders and bladder mesenchyma plus urothelium recombinants in contrast to bladder mesenchyma alone, which had no alpha-actin staining (morphometric smooth muscle analysis p = 0). There was no alpha-actin staining in chimeric bladders even when bladder mesenchymal grafts were placed directly in contact with host urothelium. In addition, bladder mesenchyma plus urothelial recombinants within the host bladder had less alpha-actin staining than their counterparts placed under the renal capsule (p = 0.001).
A diffusable factor most likely exists within adult rat bladders that inhibits smooth muscle differentiation.
我们之前已经表明,间充质-上皮相互作用对于膀胱平滑肌的发育是必要的。具体而言,没有胎儿或成年尿路上皮,胚胎大鼠膀胱间充质不会分化为平滑肌。尽管推测可扩散生长因子起作用,但这种相互作用的机制尚不清楚。我们的假设是成年大鼠膀胱内的可扩散因子影响平滑肌分化。
通过手术将14天胚胎大鼠膀胱间充质在平滑肌分化之前植入同基因成年宿主的逼尿肌间隙,创建嵌合膀胱,以测试宿主尿路上皮在不与胎儿膀胱间充质组织直接接触的情况下是否会诱导平滑肌分化。在浆膜与平滑肌层之间、平滑肌层与固有层之间以及与尿路上皮直接接触的固有层与尿路上皮之间创建逼尿肌下袋。对照组包括未去除尿路上皮的完整14天胚胎大鼠膀胱,以及与尿路上皮重组(直接接触)并置于膀胱逼尿肌下间隙和肾被膜下的14天胚胎膀胱间充质。
用针对平滑肌α-肌动蛋白和尿路上皮(细胞角蛋白7)的抗体进行免疫组织化学染色显示,完整胚胎膀胱和平膀胱间充质加尿路上皮重组体中有平滑肌分化,而单独的膀胱间充质没有α-肌动蛋白染色(形态计量学平滑肌分析p = 0)。即使膀胱间充质移植物直接与宿主尿路上皮接触,嵌合膀胱中也没有α-肌动蛋白染色。此外,宿主膀胱内的膀胱间充质加尿路上皮重组体的α-肌动蛋白染色比置于肾被膜下同行的少(p = 0.001)。
成年大鼠膀胱内很可能存在一种抑制平滑肌分化的可扩散因子。