PDF(Pubmed)
Abstract：
Benign Prostatic Hyperplasia (BPH) is a complex condition leading to Lower Urinary Tract Symptoms in aging men, characterized by cellular proliferation, smooth muscle dysfunction, inflammation, and fibrosis. While BPH is known to involve heightened macrophage infiltration, the specific contribution of infiltrating monocytes/macrophages to the disease mechanism remains uncertain. This research explores the impact of reducing circulating monocytes and subsequently limiting their tissue infiltration by using Ccr2 knockout (Ccr2-KO) mice. Ccr2-KO and wild type mice were implanted with testosterone and estradiol (T + E2, 25 mg + 2.5 mg) pellets. Urinary function was assessed via weekly void spot assays over 12 weeks, and prostatic macrophage levels were visualized and quantified in tissue sections using an F4/80 antibody. Additionally, Ki-67 staining was used to evaluate cell proliferation, and picrosirius red staining to assess collagen accumulation. Increased voiding frequency which developed in T + E2 mice, was significantly ameliorated in Ccr2-KO mice, however, both Ccr2-KO and wild type (WT) mice showed increased bladder weights after three month, representing a hypertrophic response to bladder outlet obstruction. T + E2 substantially increased the density of macrophages in WT but not Ccr2-KO mouse prostate. Proliferation rate, as indicated by Ki-67 positivity, was elevated in the vental and anterior prostate lobes but was only marginally reduced in Ccr2-KO mice. Most importantly, a significant prostatic collagen accumulation was observed in WT mice that was markedly reduced by Ccr2 deficiency post T + E2 treatment. The absence of Ccr2 mitigates urinary dysfunction and alters prostatic macrophage levels and collagen accumulation in steroid hormone imbalance. These findings suggest a crucial role for monocyte infiltration, giving rise to macrophages or other cell derivatives, to drive fibrosis.
摘要：
良性前列腺增生（BPH）是一种复杂的疾病，导致老年男性的下尿路症状，以细胞增殖为特征，平滑肌功能障碍，炎症,和纤维化。虽然已知BPH涉及增加的巨噬细胞浸润,浸润单核细胞/巨噬细胞对疾病机制的具体贡献仍不确定.这项研究探索了通过使用Ccr2敲除（Ccr2-KO）小鼠减少循环单核细胞并随后限制其组织浸润的影响。Ccr2-KO和野生型小鼠植入睾酮和雌二醇(T+E2,25mg+2.5mg)小丸。在12周内，通过每周的空隙点测定评估泌尿功能，使用F4/80抗体在组织切片中可视化和定量前列腺巨噬细胞水平。此外,Ki-67染色用于评估细胞增殖，和picrosiriusred染色以评估胶原蛋白的积累。T+E2小鼠的排尿频率增加，在Ccr2-KO小鼠中显著改善，然而,Ccr2-KO和野生型（WT）小鼠三个月后膀胱重量增加，代表对膀胱出口梗阻的肥大反应。T+E2显著增加WT但不增加Ccr2-KO小鼠前列腺中的巨噬细胞密度。增殖速率,如Ki-67阳性所示，在睾丸和前列腺前叶中升高，但在Ccr2-KO小鼠中仅略微降低。最重要的是,在WT小鼠中观察到显著的前列腺胶原积累,T+E2治疗后Ccr2缺乏显著降低。缺乏Ccr2减轻了泌尿功能障碍，并改变了类固醇激素失衡中的前列腺巨噬细胞水平和胶原蛋白积累。这些发现表明单核细胞浸润的关键作用，产生巨噬细胞或其他细胞衍生物，来驱动纤维化。
