The androgen receptor plays different roles in macrophage-induced proliferation in prostate stromal cells between transitional and peripheral zones of benign prostatic hypertrophy

Xu, Di; Wang, Xingjie; Jiang, Chuanwen; Ruan, Yuan; Xia, Shujie; Wang, Xiaohai

doi:10.17179/excli2017-335

Cited by 9 publications

(2 citation statements)

References 12 publications

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“…Clinical studies suggest that although serum testosterone levels decline during aging [64], androgen signaling may contribute to the occurrence and development of BPH [65][66][67]. Experimental data found that AR modulates the cellular growth of stromal cells by recruiting infiltrated macrophages [52,[68][69][70] and that prostate epithelial AR function is important for the macrophage-mediated EMT and proliferation of prostate epithelial cells, highlighting that AR could have a role in the cross-talk between macrophages and prostate epithelial cells [71]. Similarly, epidemiological, animal, and in vitro studies strongly suggest a proliferative and proinflammatory role for ERα and an antiproliferative role for ERβ in BPH development [72,73].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Caloric Restriction on Inflammatory Targets in the Prostates of Aged Rats

Rago,

Conforti,

La Russa

et al. 2024

IJMS

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Numerous animal models have demonstrated that caloric restriction (CR) is an excellent tool to delay aging and increase the quality of life, likely because it counteracts age-induced oxidative stress and inflammation. The aging process can affect the prostate in three ways: the onset of benign prostatic hyperplasia, prostatitis, and prostate cancer. In this study, we used 14 aged male Sprague Dawley rats, which were allocated into two groups, at the age of 18 months old. One group was fed ad libitum (a normal diet (ND)), and the other group followed a caloric restriction diet with a 60% decrease in intake. The rats were sacrificed at the age of 24 months. By immunohistochemical (IHC) and Western blot (WB) analyses, we studied the variations between the two groups in immune inflammation and fibrosis-related markers in aged prostate tissues. Morphological examinations showed lower levels of prostatic hyperplasia and fibrosis in the CR rats vs. the ND rats. The IHC results revealed that the prostates of the CR rats exhibited a lower immune proinflammatory infiltrate level and a reduced expression of the NLRP3 inflammasome pathway, together with significantly reduced expressions of mesenchymal markers and the profibrotic factor TGFβ1. Finally, by WB analysis, we observed a reduced expression of ERα, which is notoriously implicated in prostate stromal proliferation, and increased expressions of SOD1 and Hsp70, both exerting protective effects against oxidative stress. Overall, these data suggest that CR brings potential benefits to prostatic tissues as it reduces the physiological immune–inflammatory processes and the tissue remodeling caused by aging.

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Section: Discussionmentioning

confidence: 99%

The Effects of Caloric Restriction on Inflammatory Targets in the Prostates of Aged Rats

Rago,

Conforti,

La Russa

et al. 2024

IJMS

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“…Infiltrating macrophages were hypothesized as enhancing stromal growth and leading to BPH via AR signaling [ 23 ]. Moreover, this effect was more significant in the transitional zone [ 24 ]. In animal model, chemokine (C-C motif) ligand 3 (CCL3), also known as macrophage inflammatory protein 1-α (MIP-1α), was observed to be essential not only in the macrophages’ infiltration and migration, but also crucial in inducing stromal cells’ proliferation.…”

Section: Phloretin Bph and Pcamentioning

confidence: 99%

Phloretin in Benign Prostate Hyperplasia and Prostate Cancer: A Contemporary Systematic Review

Yang

Lin

et al. 2022

Life

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Currently, medication for benign prostate hyperplasia (BPH) and prostate cancer (PCa) are mainly based on modulating the hormone and nervous systems. However, side effects often affect patients, and might decrease their commitment to continuing the medication and lower their quality of life. Some studies have indicated that chronic inflammation might be the cause of BPH and PCa. Based on this hypothesis, the effect of phloretin, a potent anti-inflammatory and anti-oxidative flavonoid, has been researched since 2010. Results from animal and in-vitro studies, obtained from databases, also indicate that the use of phloretin in treating BPH and PCa is promising. Due to its effect on inflammatory cytokines, apoptosis or anti-apoptosis, reactive oxygen species, anti-oxidant enzymes and oxidative stress, phloretin is worthy of further study in human clinical trials regarding safety and effective dosages.

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The role of the androgen receptor in prostate development and benign prostatic hyperplasia: A review

Vickman

Franco

Moline

et al. 2020

Asian Journal of Urology

110

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Benign prostatic hyperplasia (BPH) is a benign enlargement of the prostate in which incidence increases linearly with age, beginning at about 50 years old. BPH is a significant source of morbidity in aging men by causing lower urinary tract symptoms and acute urinary retention. Unfortunately, the etiology of BPH incidence and progression is not clear. This review highlights the role of the androgen receptor (AR) in prostate development and the evidence for its involvement in BPH. The AR is essential for normal prostate development, and individuals with defective AR signaling, such as after castration, do not experience prostate enlargement with age. Furthermore, decreasing dihydrotestosterone availability through therapeutic targeting with 5α-reductase inhibitors diminishes AR activity and results in reduced prostate size and symptoms in some BPH patients. While there is some evidence that AR expression is elevated in certain cellular compartments, how exactly AR is involved in BPH progression has yet to be elucidated. It is possible that AR signaling within stromal cells alters intercellular signaling and a “reawakening” of the embryonic mesenchyme, loss of epithelial AR leads to changes in paracrine signaling interactions, and/or chronic inflammation aids in stromal or epithelial proliferation evident in BPH. Unfortunately, a subset of patients fails to respond to current medical approaches, forcing surgical treatment even though age or associated co-morbidities make surgery less attractive. Fundamentally, new therapeutic approaches to treat BPH are not currently forthcoming, so a more complete molecular understanding of BPH etiology is necessary to identify new treatment options.

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The androgen receptor plays different roles in macrophage-induced proliferation in prostate stromal cells between transitional and peripheral zones of benign prostatic hypertrophy

Cited by 9 publications

References 12 publications

The Effects of Caloric Restriction on Inflammatory Targets in the Prostates of Aged Rats

The Effects of Caloric Restriction on Inflammatory Targets in the Prostates of Aged Rats

Phloretin in Benign Prostate Hyperplasia and Prostate Cancer: A Contemporary Systematic Review

The role of the androgen receptor in prostate development and benign prostatic hyperplasia: A review

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