Year: 2021
Type: article
Abstract: Fibrogenic and inflammatory processes in the prostate are linked to the development of lower urinary tract symptoms (LUTS) in men. Our previous studies identified that osteopontin (OPN), a pro-fibrotic cytokine, is abundant in the prostate of men with LUTS, and its secretion is stimulated by inflammatory cytokines potentially to drive fibrosis. This study investigates whether the lack of OPN ameliorates inflammation and fibrosis in the mouse prostate. We instilled uropathogenic E. coli (UTI89) or saline (control) transurethrally to C57BL/6J (WT) or Spp1tm1Blh/J (OPN-KO) mice and collected the prostates one or 8 weeks later. We found that OPN mRNA and protein expression were significantly induced by E. coli-instillation in the dorsal prostate (DP) after one week in WT mice. Deficiency in OPN expression led to decreased inflammation and fibrosis and the prevention of urinary dysfunction after 8 weeks. RNAseq analysis identified that E. coli-instilled WT mice expressed increased levels of inflammatory and fibrotic marker RNAs compared to OPN-KO mice including Col3a1, Dpt, Lum and Mmp3 which were confirmed by RNAscope. Our results indicate that OPN is induced by inflammation and prolongs the inflammatory state; genetic blockade of OPN accelerates recovery after inflammation, including a resolution of prostate fibrosis.
Institution: University of Wisconsin–Madison
Language: English
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,160
Awards: Estrogen pathways in the development of prostatic fibrosis and lower urinary tract dysfunction, Cellular and molecular mediators of fibrosis in the development of urinary tract dysfunction, Elucidating hallmarks of aging in the development of lower urinary tract dysfunction (LUTD), Prostate inflammation increases collagen and voiding dysfunction, UW Comprehensive Cancer Center Support, Wisconsin Multidisciplinary K12 Urologic Research Career Development Program, Osteopontin: A Novel Mediator of prostatic inflammation and fibrosis, Reproductive and Developmental Toxicity of Dioxin
OpenAlex ID: W3214036765