Down-regulated CFTR During Aging Contributes to Benign Prostatic Hyperplasia.

Area of Science:

• Urology
• Molecular Biology
• Cell Biology

Background:

• Benign prostatic hyperplasia (BPH) is a common age-related prostate condition with unclear underlying mechanisms.
• The cystic fibrosis transmembrane conductance regulator (CFTR) is known to negatively regulate the nuclear factor-κB (NF-κB)/cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2) pathway.

Purpose of the Study:

• To investigate the role of CFTR in the pathogenesis of benign prostatic hyperplasia (BPH).
• To explore the relationship between CFTR, NF-κB/COX2/PGE2 pathway, and prostate stromal cell proliferation in BPH development.

Main Methods:

• Examined CFTR and COX2 expression in aging rat prostate tissues and human BPH samples.
• Utilized a human prostate epithelial cell line (PNT1A) to study the effects of CFTR suppression on NF-κB, COX2, and PGE2.
• Assessed the impact of PGE2 and conditioned media on prostate stromal cell proliferation and PCNA expression.

Main Results:

• Aging in rats showed decreased CFTR and increased COX2 expression.
• CFTR suppression in PNT1A cells led to elevated COX2, PGE2, and NF-κB activity.
• PGE2 and conditioned media from CFTR-inhibited cells stimulated prostate stromal cell proliferation, an effect reversible by COX2 or NF-κB inhibitors.
• Human BPH tissues exhibited down-regulated CFTR and up-regulated COX2/NF-κB.

Conclusions:

• CFTR negatively regulates PGE2 production via the NF-κB/COX2 pathway in prostate epithelial cells.
• Reduced CFTR function with aging leads to increased PGE2, promoting prostate stromal cell proliferation and potentially contributing to BPH development.