Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Hunan Key Laboratory of Angmedicine, Changsha, 410008, Hunan, China.
Mol Med. 2024 Mar 22;30(1):41. doi: 10.1186/s10020-024-00805-y.
Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland.
Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay.
In vivo, Itln-1 mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation.
The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.
良性前列腺增生（BPH）是一种常见的老年男性疾病，慢性炎症是其发展的关键因素。网膜素-1（也称为内特利丁-1，ITLN-1）是一种主要存在于小肠上皮细胞的抗炎蛋白。本研究旨在通过调节前列腺局部炎症来探讨 ITLN-1 减轻 BPH 的潜力。
我们的研究涉及两个体内实验模型。首先，使用 ITLN-1 基因敲除小鼠（Itln-1）研究 BPH 发展过程中 ITLN-1 的缺失情况。其次，使用丙酸睾酮（TP）诱导的 BPH 小鼠模型，用过表达 ITLN-1 的腺病毒进行处理。我们通过前列腺重量指数和组织学分析（包括 H&E 染色、免疫组织化学和酶联免疫吸附试验）评估 BPH 严重程度。在体外，我们通过细胞增殖试验和酶联免疫吸附试验评估 ITLN-1 对 BPH-1 细胞增殖和炎症反应的影响。
体内实验中，与野生型同窝仔相比，Itln-1 小鼠的前列腺重量指数升高，管腔面积增大，TNF-α 水平升高。相比之下，在 TP 诱导的 BPH 小鼠中过表达 ITLN-1 可降低前列腺重量指数、管腔面积和 TNF-α 水平。体外研究表明，ITLN-1 可抑制前列腺上皮细胞的增殖并减少巨噬细胞中 TNF-α 的产生，提示其抑制巨噬细胞介导的炎症的机制。
本研究表明，ITLN-1 通过减少前列腺局部炎症在抑制 BPH 发展中起重要作用。这些发现提示 ITLN-1 作为 BPH 治疗靶点的潜力。
