TY - JOUR
T1 - Bone Morphogenetic Protein 4 Signaling Regulates Epithelial Renewal in the Urinary Tract in Response to Uropathogenic Infection
AU - Mysorekar, Indira U.
AU - Isaacson-Schmid, Megan
AU - Walker, Jennifer N.
AU - Mills, Jason C.
AU - Hultgren, Scott J.
N1 - Funding Information:
We thank Doctors Thomas Hannan, Swaine Chen, and Jennifer Elam for thoughtful review of the manuscript. The Bmpr1a fx/fx mice were a kind gift of Doctor Yuji Mishina (NIEHS). We thank the Multiplexed Gene Analysis Core of the Siteman Cancer Center (supported in part by National Cancer Institute Grant P30-CA91842). This work was supported by National Institutes of Health Grant DK51406 and Office of Research on Women's Health Specialized Center of Research Grant DK64540 (to S.J.H.), K08-DK066062 and R01-DK079798 (to J.C.M.); postdoctoral support was provided by Individual National Research Service Award F32-CA108328 and a Pathway to Independence Award K99-DK080643 (to I.U.M.). The authors declare no competing financial interests.
PY - 2009/5/8
Y1 - 2009/5/8
N2 - 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. We investigate the mechanism of bladder epithelial regeneration in response to infection with uropathogenic E. coli (UPEC). Infection resulted in rapid sloughing of superficial cells, a marked inflammatory response, and a substantial spike in basal cell proliferation. In mice with induced urothelial ablation of a member of the TGF-β receptor superfamily, bone morphogenetic protein (Bmp)-4 receptor, infection led to aberrant urothelial renewal resulting from a block in USC differentiation into superficial cells. Chemical injury also caused sloughing but no inflammation or USC activation. Together, our study indicates that UPEC infection but not chemical injury activates the USC niche, and Bmp signaling is required for regulation of the USC response to infection.
AB - 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. We investigate the mechanism of bladder epithelial regeneration in response to infection with uropathogenic E. coli (UPEC). Infection resulted in rapid sloughing of superficial cells, a marked inflammatory response, and a substantial spike in basal cell proliferation. In mice with induced urothelial ablation of a member of the TGF-β receptor superfamily, bone morphogenetic protein (Bmp)-4 receptor, infection led to aberrant urothelial renewal resulting from a block in USC differentiation into superficial cells. Chemical injury also caused sloughing but no inflammation or USC activation. Together, our study indicates that UPEC infection but not chemical injury activates the USC niche, and Bmp signaling is required for regulation of the USC response to infection.
KW - MICROBIO
KW - STEMCELL
UR - http://www.scopus.com/inward/record.url?scp=65549083387&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2009.04.005
DO - 10.1016/j.chom.2009.04.005
M3 - Article
C2 - 19454350
AN - SCOPUS:65549083387
SN - 1931-3128
VL - 5
SP - 463
EP - 475
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 5
ER -