Bone morphogenetic protein 4 signaling regulates epithelial renewal in the urinary tract in response to uropathogenic infection.
Bone morphogenetic protein 4 signaling regulates epithelial renewal in the urinary tract in response to uropathogenic infection.
复制标题
DOI：
10.1016/j.chom.2009.04.005
复制
发表时间：
2009-05-08
影响因子：
30.3
通讯作者：
Hultgren SJ
中科院分区：
文献类型：
--
作者：
Mysorekar IU;Isaacson-Schmid M;Walker JN;Mills JC;Hultgren SJ
膀胱的移行上皮通常翻转缓慢，但在损伤时，经历快速再生，由基底尿上皮干细胞和/或早期祖细胞（USCs）提供燃料。对损伤反应的机制知之甚少。在此，我们探讨了膀胱上皮再生的机制，以应对感染尿路致病性大肠杆菌。大肠杆菌（UPEC）。我们发现，感染导致表层细胞迅速脱落，明显的炎症反应，基底细胞增殖大幅飙升。感染性损伤后的上皮更新部分由BMP信号转导介导。在Cre重组酶介导的Bmp 4受体Bmpr 1a消融的小鼠中，感染导致异常的尿路上皮更新，导致USC分化为浅表细胞的阻滞。硫酸鱼精蛋白（PS）对化学损伤的反应也引起脱落，但没有炎症或USC激活。总之，我们的研究表明，UPEC感染激活了USC生态位，Bmp信号传导是调节USC对感染的反应所必需的。
The transitional epithelium of the bladder normally turns over slowly but, upon injury, undergoes rapid regeneration, fueled by basal uroepithelial stem and/or early progenitor cells (USCs). Little is known about the mechanisms underlying the injury response. Here, we investigate the mechanism of bladder epithelial regeneration in response to infection with uropathogenic E. coli (UPEC). We show that infection resulted in rapid sloughing of superficial cells, a marked inflammatory response, and a substantial spike in basal cell proliferation. Epithelial renewal following infectious injury was mediated in part by Bmp signaling. In mice with Cre-recombinase-mediated ablation of the Bmp4 receptor, Bmpr1a, infection leads to aberrant urothelial renewal resulting in a block in USC differentiation into superficial cells. The response to chemical injury with protamine sulfate (PS) also caused sloughing but no inflammation or USC activation. Together, our study indicates that UPEC infection activates the USC niche, and Bmp signaling is required for regulation of the USC response to infection.
登录
查看更多内容
影响因子：
4
作者：
Foxman, B
通讯作者：
Foxman, B
影响因子：
6.4
作者：
Langermann, S;Möllby, R;Koenig, S
通讯作者：
Koenig, S
DOI：
10.1152/ajprenal.00533.2007
发表时间：
2008-06-01
影响因子：
4.2
作者：
Kurzrock, Eric A.;Lieu, Deborah K.;Isseroff, Roslyn R.
通讯作者：
Isseroff, Roslyn R.
影响因子：
3.1
作者：
Mulvey, MA;Schilling, JD;Hultgren, SJ
通讯作者：
Hultgren, SJ
影响因子：
19.6
作者：
Miyazaki, Y;Oshima, K;Ichikawa, I
通讯作者：
Ichikawa, I