Deng F M, Ding M, Lavker R M, Sun T T
The Ronald Perelman Department of Dermatology, Kaplan Comprehensive Cancer Center, New York University Medical School, New York, NY 10016, USA.
Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):154-9. doi: 10.1073/pnas.98.1.154.
Mammalian bladder epithelium functions as an effective permeability barrier. We demonstrate here that this epithelium can also function as a secretory tissue directly involved in modifying urinary protein composition. Our data indicate that normal bovine urothelium synthesizes, as its major differentiation products, two well-known proteases: tissue-type plasminogen activator and urokinase, as well as a serine protease inhibitor, PP5. Moreover, we demonstrate that the urothelium secretes these proteins in a polarized fashion into the urine via a cAMP- and calcium-regulated pathway. Urinary plasminogen activators of ruminants are therefore urothelium derived rather then kidney derived as in some other species; this heterogeneity may have evolved in response to different physiological or dietary factors. In conjunction with our recent finding that transgenic mouse urothelium can secrete ectopically expressed human growth hormone into the urine, our data establish that normal mammalian urothelium can function not only as a permeability barrier but also as a secretor of urinary proteins that can play physiological or pathological roles in the urinary tract.
哺乳动物膀胱上皮作为一种有效的渗透屏障发挥作用。我们在此证明，这种上皮还可作为一种分泌组织，直接参与改变尿液蛋白质组成。我们的数据表明，正常牛膀胱上皮合成两种著名的蛋白酶——组织型纤溶酶原激活物和尿激酶，以及一种丝氨酸蛋白酶抑制剂PP5，作为其主要分化产物。此外，我们证明膀胱上皮通过cAMP和钙调节途径以极化方式将这些蛋白质分泌到尿液中。因此，反刍动物尿液中的纤溶酶原激活物来源于膀胱上皮，而不像其他一些物种那样来源于肾脏；这种异质性可能是为响应不同的生理或饮食因素而进化形成的。结合我们最近的发现，即转基因小鼠膀胱上皮可将异位表达的人生长激素分泌到尿液中，我们的数据证实，正常哺乳动物膀胱上皮不仅可作为渗透屏障发挥作用，还可作为尿液蛋白质的分泌者，这些蛋白质可在尿路中发挥生理或病理作用。
