Osteopontin Deficiency Ameliorates Prostatic Fibrosis and Inflammation

Area of Science:

• Urology
• Immunology
• Fibrosis Research

Background:

• Prostate fibrotic and inflammatory processes contribute to lower urinary tract symptoms (LUTS).
• Osteopontin (OPN), a pro-fibrotic cytokine, is elevated in the prostate of men with LUTS and may be stimulated by inflammation to promote fibrosis.

Purpose of the Study:

• To investigate if the absence of OPN can alleviate inflammation and fibrosis in a mouse model of prostate injury.
• To determine the role of OPN in the inflammatory response and subsequent fibrotic changes in the prostate.

Main Methods:

• Transurethral instillation of uropathogenic E. coli (UTI89) or saline in wild-type (WT) and osteopontin-deficient (OPN-KO) mice.
• Prostate tissue collection at one and 8 weeks post-instillation for analysis of OPN expression, inflammation, and fibrosis.
• RNA sequencing (RNAseq) and RNAscope were used to analyze gene expression profiles.

Main Results:

• E. coli instillation significantly induced OPN mRNA and protein in the prostates of WT mice.
• OPN-deficient mice exhibited reduced inflammation and fibrosis compared to WT mice.
• Genetic blockade of OPN accelerated recovery from inflammation and promoted the resolution of prostate fibrosis, preventing urinary dysfunction.

Conclusions:

• Osteopontin is induced by inflammation and contributes to its persistence in the prostate.
• Targeting OPN may be a therapeutic strategy to mitigate prostate inflammation, fibrosis, and associated urinary dysfunction.