Presentation Authors: Laura Pascal*, Shinsuke Mizoguchi, Rajiv Dhir, Wei Chen, Ke Wang, Joel Nelson, Pittsburgh, PA, Daniel Metzger, Pierre Chambon, Illkirch, France, Naoki Yoshimura, Zhou Wang, Pittsburgh, PA
Introduction: Chronic inflammation is thought to contribute to the development of prostatitis and benign prostatic hyperplasia (BPH). In the prostate, the epithelial barrier functions to provide a selectively permeable barrier which serves as an interface between the glandular lumen and the underlying tissues. E-cadherin is an important adherens junction that helps to maintain the epithelial barrier in mucous membranes. This study explored the potential impact of reduced barrier function induced by deletion of E-cadherin in the murine prostate.
Methods: The PSA-CreERT2 transgenic mouse strain expressing tamoxifen-inducible CreERT2 recombinase driven by a 6-kb human PSA promoter/enhancer was crossed with the B6.129-Cdh1tm2Kem/J mouse to generate bigenic PSA-CreERT2/Cdh1-/- mice. Deletion of E-cadherin was performed by transient administration of tamoxifen when mice reached sexual maturity (7 weeks of age). Void Spot Assays and cystometry were used to assess bladder function. Mice were examined histologically at 150 days and 365 days of age.
Results: Mice with Cdh1 deletion had increased proliferation, inflammation, and stromal fibrosis at 150 days of age, as well as potential changes in bladder voiding. These alterations persisted at 365 days of age, suggesting that the loss of E-cadherin could contribute to the development of a chronically inflamed prostate.
Conclusions: These findings suggest that loss of epithelial barrier integrity in the prostate could result in chronic inflammation and the development of stromal fibrosis, inflammation and benign epithelial hyperplasia characteristic of BPH and prostatitis.
Source of Funding: This work was funded in part by National Institutes of Health Grants 1U54 DK112079, 1R56 DK107492 and R50 CA211242. This project used the Biospecimen Core and was supported in part by award P30 CA047904.