M2 macrophage-mediated interleukin-4 signalling induces myofibroblast phenotype during the progression of benign prostatic hyperplasia.
M2 macrophage-mediated interleukin-4 signalling induces myofibroblast phenotype during the progression of benign prostatic hyperplasia.
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M2巨噬细胞介导的白细胞介素4信号传导在良性前列腺增生进展过程中诱导肌成纤维细胞表型
DOI：
10.1038/s41419-018-0744-1
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发表时间：
2018-07-09
影响因子：
9
通讯作者：
Jin J
中科院分区：
文献类型：
--
作者：
Sheng J;Yang Y;Cui Y;He S;Wang L;Liu L;He Q;Lv T;Han W;Yu W;Hu S;Jin J
良性前列腺增生（BPH）是老年男性的一种进展性疾病，但加速其进展的潜在因素在很大程度上仍不明确。本研究的目的是通过了解导致早发性前列腺增生的复杂机制来阐明影响BPH进展的因素，早发性前列腺增生进展迅速，在50岁之前就需要手术干预。收集了三组人类前列腺组织样本，分别来自早发性前列腺增生患者、年龄匹配的前列腺组织和老年前列腺增生组织（每组n = 25）。我们对这些组织进行了比较，以确定前列腺增生进展的组织学特征和分子机制。我们发现，与年龄匹配的前列腺组织和老年前列腺增生组织相比，早发性前列腺增生样本的特征是基质异常过度增殖、胶原沉积以及M2巨噬细胞浸润增加。M2巨噬细胞 - 成纤维细胞共培养系统表明，肌成纤维细胞表型仅在来自早发性前列腺增生样本的成纤维细胞中被强烈诱导，而共培养的M2巨噬细胞表达高水平的促纤维化细胞因子，如白细胞介素 - 4（IL - 4）和转化生长因子β1（TGFβ1）。M2巨噬细胞衍生的IL - 4，而非TGFβ1，通过早发性前列腺增生前列腺成纤维细胞中的JAK/STAT6、PI3K/AKT和MAPK/ERK信号通路选择性地诱导肌成纤维细胞表型。综上所述，我们的结果表明，肌成纤维细胞表型的诱导可能通过M2巨噬细胞介导的IL - 4信号传导导致前列腺增生进展，并且IL - 4可能代表一个潜在的治疗靶点，有助于预防M2巨噬细胞激活以及成纤维细胞向肌成纤维细胞分化。
Benign prostatic hyperplasia (BPH) is a progressive disease in elderly men, but potential factors accelerating its progression remain largely unknown. The aim of this study was to elucidate the factors affecting BPH progression by understanding the complex mechanisms causing early- progressed BPH, which progresses rapidly and requires surgical intervention before the age of 50. Three groups of human prostate tissue samples, from patients with early-progressed BPH, age-matched prostate and elderly BPH tissues, were collected (n= 25 each). We compared these tissues to determine the histologic features and molecular mechanisms underlying BPH progression. We found that early-progressed BPH samples were characterised by aberrant stromal hyper-proliferation, collagen deposition and increased M2 macrophage infiltration, compared to those from age-matched prostate and elderly BPH tissues. The M2 macrophage–fibroblast co-culture system demonstrated that the myofibroblast phenotypes were strongly induced only in fibroblasts from the early-progressed BPH samples, while the co-cultured M2 macrophages expressed high levels of pro-fibrotic cytokines, such as IL4 and TGFβ1. M2 macrophage-derived IL4, but not TGFβ1, selectively induced the myofibroblast phenotype through the JAK/STAT6, PI3K/AKT and MAPK/ERK signalling pathways in the early-progressed BPH prostate fibroblasts. Taken together, our results indicate that induction of the myofibroblast phenotype may lead to BPH progression through M2 macrophage-mediated IL4 signalling, and that IL4 may represent a potential therapeutic target, allowing the prevention of M2 macrophage activation and fibroblast-to-myofibroblast differentiation.
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影响因子：
5
作者：
Chomarat, P;Banchereau, J
通讯作者：
Banchereau, J
影响因子：
23.4
作者：
Anderson, JB;Roehrborn, CG;Emberton, M
通讯作者：
Emberton, M
影响因子：
11.2
作者：
Franco OE;Jiang M;Strand DW;Peacock J;Fernandez S;Jackson RS 2nd;Revelo MP;Bhowmick NA;Hayward SW
通讯作者：
Hayward SW
影响因子：
6.6
作者：
通讯作者：
--
影响因子：
3.8
作者：
McCormick SM;Heller NM
通讯作者：
Heller NM