TY - JOUR
TI - Notch controls urothelial integrity in the mouse bladder
AU - Paraskevopoulou, V.
AU - Bonis, V.
AU - Dionellis, V.S.
AU - Paschalidis, N.
AU - Melissa, P.
AU - Chavdoula, E.
AU - Vasilaki, E.
AU - Pateras, I.S.
AU - Klinakis, A.
JO - JCI INSIGHT
PY - 2020
VL - 5
TODO - 3
SP - null
PB - American Society for Clinical Investigation
SN - null
TODO - 10.1172/jci.insight.133232
TODO - alpha4 integrin;  Notch receptor, animal cell;  animal experiment;  animal model;  animal tissue;  Article;  bladder;  bladder tissue;  cell interaction;  controlled study;  cystalgia;  down regulation;  extracellular matrix;  female;  gene inactivation;  genetic profile;  human;  human cell;  human tissue;  in vivo study;  interstitial cystitis;  male;  mouse;  mucosa inflammation;  nonhuman;  signal transduction
TODO - The Notch signaling pathway mediates cell-cell communication regulating cell differentiation and proliferation and cell fate decisions in various tissues. In the urinary bladder, Notch acts as a tumor suppressor in mice, while mutations in Notch pathway components have been identified in human bladder cancer as well. Here we report that the genetic inactivation of Notch in mice leads to downregulation of cell-cell and cell-ECM interaction components, including proteins previously implicated in interstitial cystitis/bladder pain syndrome (IC/BPS), structural defects and mucosal sloughing, inflammation, and leaky urine-blood barrier. Molecular profiling of ailing mouse bladders showed similarities with IC/BPS patient tissue, which also presented low Notch pathway activity as indicated by reduced expression of canonical Notch targets. Urothelial integrity was reconstituted upon exogenous reactivation of the Notch pathway, implying a direct involvement of Notch. Despite damage and inflammation, urothelial cells failed to proliferate, uncovering a possible role for α4 integrin in urothelial homeostasis. Our data uncover a broad role for Notch in bladder homeostasis involving urothelial cell crosstalk with the microenvironment. © 2020, American Society for Clinical Investigation.
ER -