Steroid hormone imbalance drives macrophage infiltration and Spp1/osteopontin + foam cell differentiation in the prostate.
Petra PopovicsKegan O SkalitzkyElise SchroederAsha JainSamara V SilverFrancesca Van FritzKristen S UchtmannChad M VezinaWilliam A RickePublished in: The Journal of pathology (2023)
Benign Prostatic Hyperplasia (BPH) occurs progressively with aging in men and drives deteriorating symptoms collectively known as Lower Urinary Tract Symptoms (LUTS). Age associated changes in circulating steroid hormones, and prostate inflammation have been postulated in the etiology of BPH/LUTS. The link between hormones and inflammation in the development of BPH/LUTS is conflicting because they may occur independently or as sequential steps in disease pathogenesis. This study aimed to decipher the prostatic immune landscape in a mouse model of lower urinary tract dysfunction (LUTD). Steroid hormone imbalance was generated by the surgical implantation of testosterone (T) and estradiol (E2) pellets into male C57BL/6J mice and gene expression analysis was performed on ventral prostates (VP). These experiments identified an increase in the expression of macrophage markers and Spp1/osteopontin (OPN). Localization studies of OPN pinpointed that OPN+ macrophages travel to the prostate lumen and transition into lipid accumulating foam cells. We also observed a significantly increase in number of tissue macrophages in the VP which was prevented in OPN knockout (OPN-KO) mice. In contrast, mast cells, but not macrophages, were significantly elevated in the dorsal prostate of T+E2 treated mice which was diminished in OPN-KO mice. Steroid hormone implantation progressively increased urinary frequency, which was ameliorated in OPN-KO mice. Our study underscores the role of age associated steroid hormone imbalances as a mechanism of expanding the prostatic macrophage population, their luminal translocation and foam cell differentiation. This article is protected by copyright. All rights reserved.
Keyphrases
- benign prostatic hyperplasia
- lower urinary tract symptoms
- high fat diet induced
- mouse model
- adipose tissue
- oxidative stress
- spinal cord
- magnetic resonance
- wild type
- computed tomography
- poor prognosis
- induced apoptosis
- insulin resistance
- magnetic resonance imaging
- genome wide
- dna methylation
- skeletal muscle
- gene expression
- cell death
- endoplasmic reticulum stress
- long non coding rna
- estrogen receptor
- sleep quality
- binding protein
- depressive symptoms
- replacement therapy