斯特罗马尔类固醇5α降解酶2通过WNT5A促进前列腺生长-淋巴细胞增强结合因子1-类似胰岛素的生长因子1信号在良性前列腺增生
Christina Sharkey1, Boqing Gu1, Xingbo Long2
1Division of Urology, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
The American journal of pathology
|September 14, 2025
概括
类固醇5α-减少酶2 (SRD5A2) 通过调节体WNT5A和IGF1信号,独立于雄激素水平,显著影响前列腺体积. 这一发现为良性前列腺增生提供了新的治疗途径.
科学领域:
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 类固醇5α-减少酶2 (SRD5A2) 对于雄激素代谢至关重要,也是良性前列腺增生症 (BPH) 的治疗点.
- 基线SRD5A2表达和前列腺体积之间的确切关系尚未完全理解.
- 在影响前列腺生长的树皮-上皮相互作用中SRD5A2的作用需要进一步阐明.
研究的目的:
- 为了研究SRD5A2表达和前列腺体积之间的相关性.
- 探索将SRD5A2与前列腺生长联系在一起的分子机制,特别是其与WNT5A和胰岛素样生长因子1 (IGF1) 信号的相互作用.
- 确定BPH的新型治疗点,特别是在对传统疗法耐药的情况下.
主要方法:
- 从临床试验和生物存储库中对人类前列腺组织中SRD5A2表达的分析.
- 对SRD5A2,WNT5A,前列腺体积和信号通路的定量评估和相关性分析.
- 使用Srd5a2-null小鼠的体内研究和在前列腺 stromal 细胞中涉及SRD5A2过度表达的体内实验.
主要成果:
- SRD5A2表达与前列腺总体和过渡区体积有很强的相关性.
- 流体WNT5A的表达与SRD5A2具有积极的关联,但二二的水平没有.
- 过度表达SRD5A2可以调节WNT5A和IGF1的信号传递,促进树皮细胞的增殖和膜上皮的生长.
结论:
- SRD5A2通过一个侧膜WNT5A-IGF1对线信号轴驱动前列腺生长,独立于雄激素水平.
- 这一途径代表了良性前列腺增生的一个新的治疗机制.
- 研究结果表明,BPH患者对标准的5α-减少酶抑制剂治疗有抗性的潜在治疗方法.
相关概念视频
03:03mTOR Signaling and Cancer Progression
4.6K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.6K
01:16TGF - β Signaling Pathway
10.5K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.5K
02:54Canonical Wnt Signaling Pathway
10.4K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.4K
02:23Abnormal Proliferation
5.1K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.1K
01:22PI3K/mTOR/AKT Signaling Pathway
5.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.4K
01:24Regulation of Angiogenesis and Blood Supply
3.3K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.3K