One of the central goals of the Popovics Lab is to dissect the role of the immune environment in driving BPH. One of our recent key findings is that macrophages migrate to the prostate lumen, where they take up lipids and become foam cells. We identified that these cells express genes that encode known secreted pathological factors, including VEGF, TGF-β1 and osteopontin, proposing an unfavorable role for this cell type. We also recognized a marked increase in the expression of CXCL17, a known monocyte attractant, in epithelial cells, suggesting that this might be a key molecule driving luminal translocation of macrophages. Finally, we found increased overall lipid accumulation in BPH compared to healthy prostate, implying lipid dysregulation as a new feature in pathogenesis. Our R01-funded projects will focus on addressing these hypotheses in the next 5 years in collaboration with Drs. Elena Galkina and Julius Nyalwidhe.

Pro-inflammatory signals in prostate disease

Expressional analysis of prostates from mice with steroid hormone-induced LUTD identified serum amyloid A (SAA1/2) and osteopontin as key upregulated pro-inflammatory genes. Our studies suggest that osteopontin is important for macrophage infiltration, epithelial proliferation and fibrosis. Future studies will further examine the role of osteopontin via testing an antagonistic therapy as well as its overexpression in prostate regeneration experiments. 

In contrast, there is much less known about the role of SAAs. Our current studies aim to decipher whether there is an increased SAA level in LUTS/BPH prostates as well as determine its downstream signaling and physiological role in the prostate.