S100A4 modulates cell proliferation, apoptosis and fibrosis in the hyperplastic prostate

Area of Science:

• Urology
• Cell Biology
• Molecular Medicine

Background:

• Benign prostatic hyperplasia (BPH) is a prevalent condition in aging men, causing lower urinary tract symptoms (LUTS).
• The precise molecular mechanisms underlying BPH pathogenesis remain incompletely understood.
• S100 calcium binding protein A4 (S100A4) is implicated in cellular processes relevant to disease, including proliferation and apoptosis.

Purpose of the Study:

• To investigate the role of S100 calcium binding protein A4 (S100A4) in the development of benign prostatic hyperplasia (BPH).
• To elucidate the signaling pathways through which S100A4 influences prostate tissue.

Main Methods:

• Utilized human prostate cell lines, primary rat cells, human tissues, and established BPH rat models.
• Assessed S100A4 expression and localization using qRT-PCR, immunofluorescence, Western blotting, and immunohistochemistry.
• Created S100A4 knockdown/overexpression models and treated BPH rats with the S100A4 inhibitor Niclosamide.

Main Results:

• S100A4 expression was elevated in BPH tissues and localized to prostatic stroma and epithelium.
• S100A4 knockdown induced apoptosis, inhibited proliferation, and reduced fibrosis markers.
• S100A4 overexpression reversed these effects, implicating the ERK and Wnt/β-catenin pathways.

Conclusions:

• S100 calcium binding protein A4 (S100A4) significantly contributes to benign prostatic hyperplasia (BPH) development.
• S100A4 modulates cell proliferation, apoptosis, and fibrosis through ERK and Wnt/β-catenin signaling.
• S100A4 represents a potential novel therapeutic target for BPH.