良性前列腺增生症(benign prostatic hyperplasia ,BPH)是一种常见的男性疾病,其发病基础是老年和具有功能的睾丸,但是迄今为止,其发病机制尚未完全明了。上皮间质转化(epithelial-mesenchymal transition ,EMT)直接参与恶性肿瘤发生发展,其涉及细胞从上皮细胞向间充质细胞的转化,伴随着细胞形态的改变、细胞间相互作用的调节以及细胞的迁移和侵袭。近年来研究提示EMT是前列腺增生的一个关键过程,在前列腺增生的发生发展中起到重要作用,可以通过影响细胞的增殖、存活、衰老、代谢和免疫等生理过程,进而影响前列腺组织的生长和重构。其中,研究发现调节EMT的磷脂酰肌醇3-激酶(phosphatidylinostol 3-lcinases ,PI3K)/蛋白激酶b信号通路(AKT)和转化生长因子β信号通路(transforming groweh factor-β , TGF-β)等,可以对前列腺增生的发生发展产生重要影响。因此,深入研究EMT在前列腺增生中的作用机制,有助于发掘新的治疗靶点,本综述旨在深入探讨EMT在前列腺增生发病机制中的关键作用,着重强调细胞信号通路在良性前列腺增生EMT的机制,为未来研究和治疗提供了有益的参考和洞察,为疾病的预防和治疗提供新的思路。
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[1] LANGAN RC. Benign prostatic hyperplasia [J]. Prim Care, 2019, 46(2): 223-232.
[2] EGAN KB. The epidemiology of benign prostatic hyperplasia associated with lower urinary tract symptoms: prevalence and incident rates [J]. Urol Clin North Am, 2016, 43(3): 289-297.
[3] L IM KB. Epidemiology of clinical benign prostatic hyperplasia [J]. Asian J Urol, 2017, 4(3): 148-151.
[4] ROBERT G, DE LA TAILLE A, DESCAZEAUD A. Données épidémiologiques en rapport avec la prise en charge de l’HBP [Epidemiology of benign prostatic hyperplasia] [J]. Prog Urol, 2018, 28(15): 803-812.
[5] WANG YB, YANG L, DENG YQ, et al. Causalrelationship between obesity, lifestyle factors and risk of benign prostatic hyperplasia: a univariable and multivariable mendelian randomization study [J]. J Transl Med, 2022, 20(1): 495.
[6] CHEN B, CAO D, CHEN Z, et al. Estrogen regulates the proliferation and inflammatory expression of primary stromal cell in benign prostatic hyperplasia [J]. Transl Androl Urol, 2020, 9(2): 322-331.
[7] ANGRIMANI DSR, BRITO MM, RUI BR, et al. Reproductive and endocrinological effects of benign prostatic hyperplasia and finasteride therapy in dogs [J]. Sci Rep, 2020, 10(1): 14834.
[8] LI Y, SHI B, DONG F, et al. Effects of inflammatory responses, apoptosis, and STAT3/NF- κB- and Nrf2- mediated oxidative stress on benign prostatic hyperplasia induced by a high-fat diet [J]. Aging (Albany NY), 2019, 11(15): 5570-5578.
[9] SONG W, LI DY, YUAN HC, et al. Relationship between interleukin-8 levels in expressed prostatic secretion and expressions of bFGF and Bcl- 2 in benign prostatic hyperplasia [J]. Zhonghua Yi Xue Za Zhi, 2016, 96(2): 104-107.
[10] HENNENBERG M, SCHREIBER A, CIOTKOWSKA A, et al. Cooperative effects of EGF, FGF, and TGF-β1 in prostate stromal cells are different from responses to single growth factors [J]. Life Sci, 2015, 123: 18-24.
[11] ALONSO- MAGDALENA P, BRÖSSNER C, REINER A, et al. A role for epithelial- mesenchymal transition in the etiology of benign prostatic hyperplasia [J]. Proc Natl Acad Sci U S A, 2009, 106(8): 2859-2863.
[12] CHEN S, ZHU J, ZUO S, et al. 1,25(OH)2D3 attenuates TGF-β1/β2- induced increased migration and invasion via inhibiting epithelial- mesenchymal transition in colon cancer cells [J]. Biochem Biophys Res Commun, 2015, 468(1- 2): 130-135.
[13] DONGRE A, WEINBERG RA. New insights into the mechanisms of epithelial- mesenchymal transition and implications for cancer [J]. Nat Rev Mol Cell Biol, 2019, 20(2): 69-84.
[14] MENG Z, YANG T, LIU D. Type- 2 epithelial-mesenchymal transition in oral mucosal nonneoplastic diseases [J].Front Immunol, 2022, 13: 1020768.
[15] PASTUSHENKO I, BLANPAIN C. EMT transition states during tumor progression and metastasis [J]. Trends Cell Biol, 2019, 29(3): 212-226.
[16] DEBNATH P, HUIREM RS, DUTTA P, et al. Epithelialmesenchymal transition and its transcription factors [J]. Biosci Rep, 2022, 42(1): BSR20211754.
[17] PENG D, FU M, WANG M, et al. Targeting TGF-β signal transduction for fibrosis and cancer therapy [J]. Mol Cancer, 2022, 21(1): 104.
[18] SLABÁKOVÁ E, PERNICOVÁ Z, SLAVÍČKOVÁ E, et al. TGF-β1- induced EMT of non- transformed prostate hyperplasia cells is characterized by early induction of SNAI2/Slug [J]. Prostate, 2011, 71(12): 1332-1343.
[19] HUANG X, LEE C. Regulation of stromal proliferation, growth arrest, differentiation and apoptosis in benign prostatic hyperplasia by TGF- beta [J]. F ront Biosci, 2003, 8: s740-749.
[20] LA VIGNERA S, CONDORELLI RA, RUSSO GI, et al. Endocrine control of benign prostatic hyperplasia [J]. Andrology, 2016, 4(3): 404-411.
[21] WANG L, CAO Y, GUAN Z, et al. Prostatic epithelial cells and their high expressions of CK IP- 1 affect the TGF- β1expression levels which might reduce the scar formation in remodeling stage at prostatic urethral wounds after wound repair [J]. Int Urol Nephrol, 2020, 52(1): 97- 106.
[22] KIM HJ, JIN BR, AN HJ. Hesperidin ameliorates benign prostatic hyperplasia by attenuating cell proliferation, inflammatory response, and epithelial-mesenchymal transition via the TGF-β1/ Smad signaling pathway [J]. Biomed Pharmacother, 2023, 160: 114389.
[23] CHEN Y, XU H, LIU C, et al. LncRNA DIO3OS regulated by TGF- β1 and resveratrol enhances epithelial mesenchymal transition of benign prostatic hyperplasia epithelial cells and proliferation of prostate stromal cells [J]. Transl Androl Urol, 2021, 10(2): 643-653.
[24] TONG S, MO M, HU X, et al. MIR663AHG as a competitive endogenous RNA regulating TGF- β- induced epithelial proliferation and epithelial- mesenchymal transition in benign prostate hyperplasia [J]. J Biochem Mol Toxicol, 2023, 37(9): e23391.
[25] YOOK JI, L I XY, OTA I, et al. A W nt- Axin2- GSK3 beta cascade regulates snail1 activity in breast cancer cells [J]. Nat Cell Biol, 2006, 8(12): 1398-1406.
[26] 黄明, 王娜. 脂肪来源干细胞通过 Wnt/β-catenin通路调控前列 腺增生上皮 BPH-1细胞的增殖和凋亡[J]. 基因组学与应用生物 学, 2019, 38(8): 3857-3862.
[27] WANG Y, SHI J, CHAI K, et al. The role of snail in EMT and tumorigenesis [J]. Curr Cancer Drug Targets, 2013, 13(9): 963-972.
[28] SHAN S, SU M, LI Y, et al. Mechanism of RhoA regulating benign prostatic hyperplasia: RhoA- ROCK- β- catenin signaling axis and static & dynamic dual roles [J]. Mol Med, 2023, 29(1): 139.
[29] LEE JS, KIM HY, JEONG NY, et al. Expression of αBcrystallin overrides the anti- apoptotic activity of XIAP [J]. Neuro Oncol, 2012, 14(11): 1332-1345.
[30] VICHALKOVSKI A, GRESKO E, HESS D, et al. PKB/ AKT phosphorylation of the transcription factor Twist- 1 at Ser42 inhibits p53 activity in response to DNA damage [J]. Oncogene, 2010, 29(24): 3554-3565.
[31] LEE YJ, HAN HJ. Troglitazone ameliorates high glucoseinduced EMT and dysfunction of SGLTs through PI3K/ Akt,GSK- 3β, Snail1, and β- catenin in renal proximal tubule cells [J]. Am J Physiol Renal Physiol, 2010, 298(5): F1263-1275.
[32] HONG KO, KIM JH, HONG JS, et al. Inhibition of Akt activity induces the mesenchymal- to- epithelial reverting transition with restoring E- cadherin expression in KB and KOSCC-25B oral squamous cell carcinoma cells [J]. J Exp Clin Cancer Res, 2009, 28(1): 28.
[33] MAJUMDER PK, SELLERS WR. Akt-regulated pathways in prostate cancer [J]. Oncogene, 2005, 24(50): 7465-7474.
[34] SHORNING BY, DASS MS, SMALLEY MJ, et al. The PI3K- AKT- mTOR pathway and prostate cancer: at the crossroads of AR, MAPK, and WNT signaling [J]. Int J Mol Sci, 2020, 21(12): 4507.
[35] EL- SAHAR AE, BEKHIT N, EISSA NM, et al. Targeting HMGB1/PI3K/Akt and NF- κB/Nrf- 2 signaling pathways by vildagliptin mitigates testosterone- induced benign prostate hyperplasia in rats [J]. Life Sci, 2023, 1;322: 121645.
[36] WANG L, LIN N, LI Y. The PI3K/AKT signaling pathway regulates ABCG2 expression and confers resistance to chemotherapy in human multiple myeloma [J]. Oncol Rep, 2019, 41(3): 1678-1690.
[37] REENIVASULU K, NANDEESHA H, DORAIRAJAN LN, et al. Over expression of PI3K- AkT reduces apoptosis and increases prostate size in benign prostatic hyperplasia [J]. Aging Male, 2020, 23(5): 440-446.
[38] CHEN Y, XU H, SHI Q, et al. Hypoxia-inducible factor 1α (HIF- 1α) mediates the epithelial- mesenchymal transition in benign prostatic hyperplasia [J]. Int J Clin Exp Pathol, 2019, 1;12(1): 295-304.
[39] WANG HY, ZHANG XP, WANG W. Regulation of epithelial- to- mesenchymal transition in hypoxia by the HIF-1α network [J]. FEBS Lett, 2022, 596(3): 338-349.
杨保全,丁森泰.上皮间质转化在前列腺增生发病机制中的作用[J].泌尿外科杂志(电子版),2024,16(01):59-64.DOI:10.20020/j.CNKI.1674-7410.2024.01.13.
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良性前列腺增生症(benign prostatic hyperplasia, BPH)是一种常见的男性疾病,其临床表现主要为下尿路症状(lower urinary tract symptoms,LUTS),例如尿频和排尿困难等[1]。组织学上主要表现为前列腺间质和腺体成分的增生。该病通常会随着年龄的增长而发生,且据统计,其全球患病率逐年上升,成为男性健康领域中的重要问题之一。在不同地区和族群之间,前列腺增生的发病率存在差异。前列腺增生的发病率随着年龄的增长逐渐升高。50岁以上男性BPH患病率为50%~70%,并随着年龄的增长而增加,70岁以上BPH患病率超过80%[2]。研究表明,BPH患病率在各地有显著的差异,欧美国家的BPH患病率通常较高,尤其是在西方国家的老年男性中。相比之下,亚洲国家的患病率通常较低,特别是在东南亚地区[3]。BPH的发病率与生活方式和环境因素也有关系,研究表明,饮食结构、运动习惯、吸烟和饮酒等生活方式因素与前列腺增生的发病率相关[4]。此外,前列腺增生的发病率还与其他危险因素如高血压、糖尿病、肥胖等因素有关[5]。本综述旨在深入探讨上皮间质转化(epithelial-mesenchymal transition ,EMT)在BPH发病机制中的关键作用。着重强调细胞信号通路在BPH中EMT的机制。
1 前列腺增生发病机制
2 上皮间质转化
3 TGF-β信号通路在BPH中作用
4 Wnt/β-catenin信号通路在BPH中作用
5 PI3K-AKT信号通路在BPH中作用
6 缺氧诱导因子-1α与 EMT 在 BPH 中的作用
众多研究发现EMT在前列腺增生中起着重要作用,其参与了BPH的发病和进展过程。因此,研究EMT在BPH中的作用,对于临床治疗和诊断具有重要意义。本文探讨了EMT在前列腺增生中的作用机制,并着重分析了TGF-β/Smad信号通路、Wnt/β-catenin和PI3K-AKT信号通路以及缺氧诱导因子在其中的作用。结论表明,EMT在前列腺增生的发生和发展中起着重要作用,不仅影响前列腺细胞的增殖和分化,还参与了前列腺组织的重塑和侵袭。缺氧环境下HIF-1α的表达与EMT各信号通路的同步激活,可能是最终导致前列腺增生的重要发病机制。因此,针对EMT相关的信号通路和分子机制的治疗策略可能会成为前列腺增生的新治疗方法。此外,EMT的生物标志物在前列腺增生的早期诊断和预后评估中也具有潜在的应用价值。尽管EMT在BPH的发病机制的标记物、信号通路以及相关蛋白有待进一步深入研究,但EMT在前列腺增生的诊治中具有广阔的应用前景,值得深入研究和探索。
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