Research Paper Volume 14, Issue 7 pp 2945—2965

E-cadherin deficiency promotes prostate macrophage inflammation and bladder overactivity in aged male mice

Laura E. Pascal1,2,3, , Taro Igarashi1, , Shinsuke Mizoguchi1, , Wei Chen1, , Lora H. Rigatti4, , Caroline G. Madigan2, , Rajiv Dhir5, , Wade Bushman6, , Donald B. DeFranco2,7, , Naoki Yoshimura1, , Zhou Wang1,2,3, ,

  • 1 Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA
  • 2 Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA
  • 3 UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA
  • 4 Division of Laboratory Animal Resources, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA
  • 5 Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA
  • 6 Department of Urology, University of Wisconsin, Madison, WI 53705, USA
  • 7 Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA

Received: December 23, 2021       Accepted: March 9, 2022       Published: March 31, 2022      

https://doi.org/10.18632/aging.203994
How to Cite

Copyright: © 2022 Pascal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Decreased E-cadherin immunostaining is frequently observed in benign prostatic hyperplasia (BPH) and was recently correlated with increased inflammation in aging prostate. Homozygous E-cadherin deletion in the murine prostate results in prostate inflammation and bladder overactivity at 6 months of age. However, this model is limited in that while E-cadherin is significantly reduced in BPH, it is not completely lost; BPH is also strongly associated with advanced age and is infrequent in young men. Here, we examined the functional consequences of aging in male mice with prostate luminal epithelial cell-specific E-cadherin heterozygosity. In control mice, aging alone resulted in an increase in prostate inflammation and changes in bladder voiding function indicative of bladder underactivity. At 24 months of age, mice with prostate-specific Cre-mediated heterozygous deletion of E-cadherin induced at 7 weeks of age developed additional prostatic defects, particularly increased macrophage inflammation and stromal proliferation, and bladder overactivity compared to age-matched control mice, which are similar to BPH/LUTS in that the phenotype is slow-progressing and age-dependent. These findings suggest that decreased E-cadherin may promote macrophage inflammation and fibrosis in the prostate and subsequent bladder overactivity in aging men, promoting the development and progression of BPH/LUTS.

Abbreviations

BPH: benign prostatic hyperplasia; LUTS: lower urinary tract symptoms; VP: ventral prostate; LP: lateral prostate; DP: dorsal prostate; AP: anterior prostate.