Patients with encapsulating peritoneal sclerosis have increased peritoneal expression of connective tissue growth factor (CCN2), transforming growth factor-β1, and vascular endothelial growth factor.
Patients with encapsulating peritoneal sclerosis have increased peritoneal expression of connective tissue growth factor (CCN2), transforming growth factor-β1, and vascular endothelial growth factor.
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DOI：
10.1371/journal.pone.0112050
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Boer WH
中科院分区：
文献类型：
--
作者：
Abrahams AC;Habib SM;Dendooven A;Riser BL;van der Veer JW;Toorop RJ;Betjes MG;Verhaar MC;Watson CJ;Nguyen TQ;Boer WH
包裹性腹膜硬化（EPS）是腹膜透析（PD）的一种毁灭性并发症。发病机制尚不清楚，也没有预防策略或有针对性的药物治疗。CCN2具有促纤维化和促血管生成的作用，是一个有吸引力的靶点。因此，我们研究了CCN2以及tgf - β1和VEGF在腹膜纤维化不同阶段的腹膜表达。对16例PD患者进行了调查，并与12例血液透析患者和4例预先移植患者进行了比较。此外，研究了12例EPS患者与13例PD和12例无EPS的非PD患者的表达情况。在肾移植或EPS手术期间取腹膜组织。在一部分患者中，测定了腹膜流出液和血浆中的CCN2蛋白水平。采用qPCR、组织学、免疫组织化学和ELISA检测。腹膜CCN2表达在PD患者中比预先移植患者高5倍（P<0.05），但与血液透析患者无差异。tgf - β1、VEGF在三组小鼠腹膜中的表达差异无统计学意义；腹膜厚度也没有变化。与没有EPS的PD患者相比，EPS患者腹膜CCN2（35倍，P<0.001）、tgf - β1（24倍，P<0.05）和VEGF（77倍，P<0.001）的表达增加。在EPS患者中，CCN2蛋白主要定位于腹膜内皮细胞和成纤维细胞。EPS患者腹膜流出液中CCN2蛋白水平显著高于PD患者（12.0±4.5 vs 0.91±0.92 ng/ml， P<0.01），而血浆中CCN2水平未升高。EPS患者腹膜CCN2、tgf - β1、VEGF表达显著升高。在腹膜纤维化早期，只有CCN2表达轻微升高。腹膜CCN2过表达在EPS患者是一种局部驱动的反应。CCN2作为CCN2抑制剂预防或治疗EPS的生物标志物和靶点的潜力有待进一步研究。
Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFβ1 and VEGF, in different stages of peritoneal fibrosis. Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P<0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFβ1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P<0.001), TGFβ1 (24-fold, P<0.05), and VEGF (77-fold, P<0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0±4.5 vs. 0.91±0.92 ng/ml, P<0.01), while plasma CCN2 levels were not increased. Peritoneal expression of CCN2, TGFβ1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study.
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影响因子：
4.1
作者：
Leask, Andrew;Parapuram, Sunil K.;Xu Shi-wen;Abraham, D. J.
通讯作者：
Abraham, D. J.
影响因子：
3
作者：
Liu, Yang;Li, Jian-Fei;Zhou, Xiang
通讯作者：
Zhou, Xiang
影响因子：
13.2
作者：
Barreto, Deirisa Lopes;Krediet, Raymond T.
通讯作者：
Krediet, Raymond T.
影响因子：
6.1
作者：
Leung, Joseph C. K.;Chan, Loretta Y. Y.;Lai, Kar Neng
通讯作者：
Lai, Kar Neng
DOI：
10.2215/cjn.03630807
发表时间：
2008-05-01
影响因子：
9.8
作者：
Honda, Kazuho;Hamada, Chieko;Hirano, Hiroshi
通讯作者：
Hirano, Hiroshi