Chemokines and BPH/LUTS.
Chemokines and BPH/LUTS.
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DOI：
10.1016/j.diff.2011.04.003
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发表时间：
2011-11
期刊：
影响因子：
2.9
通讯作者：
Macoska, Jill A.
中科院分区：
文献类型：
--
作者：
Macoska, Jill A.
大量已发表的研究表明，由于衰老过程或炎症反应导致正常组织内稳态的破坏，前列腺微环境会主动分泌各种趋化因子。衰老的间质成纤维细胞的积累，可能还有上皮细胞的积累，可能是人类前列腺老化和增大过程中趋化因子分泌的潜在驱动力。慢性前列腺炎/慢性盆腔疼痛综合征(CP/CPPS)和组织学炎症也可能是前列腺趋化因子分泌的丰富来源。趋化因子一旦与其同源受体结合，可以刺激强大的促增殖信号转导通路，从而在良性前列腺增生症(BPH)和下尿路症状(LUTS)的发生发展中发挥强大的生长因子作用。这些功能已经在实验中得到了充分的证明，特别是针对强大的丝裂原激活蛋白激酶(MAPK)和磷脂酰肌醇3-激酶(PI3K)信号，以及介导趋化因子刺激的细胞增殖反应的全球转录反应。一小部分文献也表明，趋化因子介导的血管生成可能是BPH/LUTS发生和发展的一个促成因素。因此，在老化的前列腺微环境中观察到的多种趋化因子的低水平分泌可能促进与前列腺体积增加相关的间质成纤维细胞和上皮细胞类型的低水平但累积的过度增殖。虽然积累的证据远不完整，并且在认识上存在一些相当广泛的差距，但它支持这样的结论，即趋化因子可以而且很可能确实促进前列腺增大和相关的下尿路症状，并证明进一步的研究将趋化因子作为潜在的治疗靶点来延缓或消融BPH/LUTS的发生和发展。
A wealth of published studies indicate that a variety of chemokines are actively secreted by the prostatic microenvironment consequent to disruptions in normal tissue homeostasis due to the aging process or inflammatory responses. The accumulation of senescent stromal fibroblasts, and, possibly, epithelial cells, may serve as potential driving forces behind chemokine secretion in the aging and enlarged human prostate. Chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS) and histological inflammation may also potentially serve as rich sources of chemokine secretion in the prostate. Once bound to their cognate receptors, chemokines can stimulate powerful pro-proliferation signal transduction pathways and thus function as potent growth factors in the development and progression of Benign Prostatic Hyperplasia (BPH) and Lower Urinary Tract Symptoms (LUTS). These functions have been amply demonstrated experimentally and particularly point to robust Mitogen Activated Protein Kinase (MAPK) and Phosphoinositide 3-kinase (PI3K) signaling, as well as global transcriptional responses, which mediate chemokine-stimulated cellular proliferative responses. A small body of literature also suggests that chemokine-mediated angiogenesis may comprise a contributing factor to BPH/LUTS development and progression. Thus, the observed low-level secretion of multiple chemokines within the aging prostatic microenvironment may promote a concomitant low-level, but cumulative, over-proliferation of both stromal fibroblastic and epithelial cell types associated with increased prostatic volume. Though the accumulated evidence is far from complete and suffers from some rather extensive gaps in knowledge, it argues favorably for the conclusion that chemokines can, and likely do, promote prostatic enlargement and the associated lower urinary tract symptoms, and justifies further investigations examining chemokines as potential therapeutic targets to delay or ablate BPH/LUTS initiation and progression.
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影响因子：
11.2
作者：
Bavik, C;Coleman, I;Nelson, PS
通讯作者：
Nelson, PS
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
2.1
作者：
DEERING, RE;BIGLER, SA;BRAWER, MK
通讯作者：
BRAWER, MK
影响因子：
2.8
作者：
DEERING, RE;BIGLER, SA;BRAWER, MK
通讯作者：
BRAWER, MK
DOI：
10.1002/pros.21081
发表时间：
2010-04-01
期刊：
The Prostate
影响因子：
--
作者：
Fujita K;Ewing CM;Getzenberg RH;Parsons JK;Isaacs WB;Pavlovich CP
通讯作者：
Pavlovich CP