Claudin-1 down-regulation in the prostate is associated with aging and increased infiltration of inflammatory cells in BPH.

Benign prostatic hyperplasia (BPH) is an age-related disease that is frequently associated with chronic prostatic inflammation. In previous studies, we detected the presence of PSA protein in the stroma of BPH nodules and down-regulation of junction proteins E-cadherin and claudin-1. Transmission electron microscopy (TEM) imaging showed a decrease in tight junctions suggesting the luminal epithelial barrier in BPH tissues may be compromised. Recent in vitro studies showed that stimulation of benign prostate epithelial cell lines with TGF-β1 induced a decrease in claudin-1 expression suggesting that inflammation might be associated with alterations in the prostate epithelial barrier. This study explored the potential associations between aging and loss of junction proteins and the presence of inflammatory cells in prostate tissue specimens from young healthy donors and aged BPH patients.

Immunostaining of serial prostate sections from 13 BPH patients and five healthy young donors was performed for claudin-1, CD4, CD8, CD20 and CD68. H-Scores and the number of inflammatory cells were calculated for the same area in donor, normal adjacent prostate (NAP) to and BPH specimens. Quantification and statistical correlation analyses were performed.

Claudin-1 immunostaining was inversely associated with increasing age, and inflammation in prostate specimens. B-cell infiltration increased with age and BPH was associated with an increased infiltration of T-cells and macrophages compared to NAP.

These findings suggest that aging is associated with down-regulation of claudin-1 and claudin-1 is further decreased in BPH. Claudin-1 down-regulation was associated with increased infiltration of inflammatory cells in both NAP and BPH tissues. Claudin-1 down-regulation in the aging prostate could contribute to increased prostatic inflammation, subsequently contributing to BPH pathogenesis.

American journal of clinical and experimental urology. 2021 Feb 15*** epublish ***

Laura E Pascal, Rajiv Dhir, Goundappa K Balasubramani, Wei Chen, Chandler N Hudson, Pooja Srivastava, Anthony Green, Donald B DeFranco, Naoki Yoshimura, Zhou Wang

Department of Urology, University of Pittsburgh School of Medicine Pittsburgh, PA, USA., Department of Pathology, University of Pittsburgh School of Medicine Pittsburgh, PA, USA., Department of Epidemiology, Epidemiology Data Center, University of Pittsburgh Pittsburgh, PA, USA., Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine Pittsburgh, PA, USA.