15-Deoxy-Delta12,14-prostaglandin J2 inhibits angiotensin II-induced fibronectin expression via hepatocyte growth factor induction in human peritoneal mesothelial cells.
15-Deoxy-Delta12,14-prostaglandin J2 inhibits angiotensin II-induced fibronectin expression via hepatocyte growth factor induction in human peritoneal mesothelial cells.
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15-Deoxy-Delta12,14-prostaglandin J2 通过人腹膜间皮细胞中的肝细胞生长因子诱导抑制血管紧张素 II 诱导的纤连蛋白表达。
DOI：
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发表时间：
2010
影响因子：
1.9
通讯作者：
N. Yorioka
中科院分区：
文献类型：
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作者：
Yukio Yokoyama;Takao Masaki;K. Kiribayashi;Ayumu Nakashima;Keiko Kokoroishi;T. Ogawa;Nobuoki Kohno;N. Yorioka
15-脱氧-三角洲(12，14)-前列腺素J(2)(15d-PGJ(2))是一种内源性过氧化物酶体增殖物激活受体γ(PPARGamma)激动剂，可抑制进行性基质沉积；然而，15d-PGJ(2)对人腹膜间皮细胞(HPMC)的影响知之甚少。我们研究了以下几个方面：(1)PPARγ的表达；(2)15d-PGJ(2)对血管紧张素II(Ang II)诱导的纤维连接蛋白(FN)表达和分泌的影响；(3)15d-PGJ(2)(有或没有Ang II以及有或没有PPARγ特异性拮抗剂GW9662)和合成PPARγ激动剂吡格列酮对肝细胞生长因子(HGF)表达和分泌的影响；(Iv)HGF对Ang II诱导的FN表达和分泌的影响；(V)c-Met(一种特异的肝细胞生长因子受体)的表达及其磷酸化信号；(Vi)肝细胞生长因子参与15d-PGJ(2)选择性c-Met抑制剂pHA-665752的作用。免疫印迹分析检测PPAR-γ的存在。15D-PGJ(2)抑制Ang II诱导的FN表达和HGF表达，GW9662可完全阻断Ang II对HGF表达的影响。此外，15d-PGJ(2)诱导的HGF分泌和吡格列酮诱导的HGF产生均有上调。我们证实了c-Met的存在，并证明肝细胞生长因子抑制Ang II诱导的Fn表达并激活c-Met的磷酸化，这一作用可被pHA-665752阻断；15d-PGJ(2)也激活c-Met的磷酸化。此外，PHA-665752可减弱15d-PgJ(2)对FN分泌的抑制作用。这些结果表明，15d-PGJ(2)对HPMC具有新的有效的抗纤维化作用，这一作用可能是由HGF介导的。
15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is an endogenous peroxisome proliferator-activated receptor gamma (PPARgamma) agonist that suppresses progressive matrix deposition; however, little is known about the effects of 15d-PGJ(2) on human peritoneal mesothelial cells (HPMCs). We investigated the following: (i) the expression of PPARgamma; (ii) the effect of 15d-PGJ(2) on angiotensin II (Ang II)-induced fibronectin (FN) expression and secretion; (iii) the effect of 15d-PGJ(2) (with or without Ang II and with or without the specific PPARgamma antagonist GW9662) and pioglitazone, a synthetic PPARgamma agonist, on hepatocyte growth factor (HGF) expression and secretion; (iv) the effect of HGF on Ang II-induced FN expression and secretion; (v) the expression of c-Met (a specific HGF receptor) and its phospho-signal; and (vi) the involvement of HGF in the effect produced by 15d-PGJ(2) using selective c-Met inhibitor PHA-665752. The presence of PPARgamma was detected by western blot analysis. 15d-PGJ(2) inhibited Ang II-induced FN expression and increased HGF expression, even in the presence of Ang II. This effect of HGF expression was completely prevented by co-treatment with GW9662. Additionally, upregulation of HGF secretion induced by 15d-PGJ(2) and HGF production induced by pioglitazone was revealed. We demonstrated the presence of c-Met, and presented evidence that HGF inhibits Ang II-induced FN expression and activates phosphorylation of c-Met, which is blocked by PHA-665752; 15d-PGJ(2) also activated c-Met phosphorylation. Furthermore, PHA-665752 attenuates the inhibitory effects of 15d-PGJ(2) on FN secretion. These findings suggest that 15d-PGJ(2) has a novel and potent antifibrotic effect in HPMC and this action is likely mediated by HGF.
影响因子：
10.5
作者：
TONTONOZ, P;HU, E;SPIEGELMAN, BM
通讯作者：
SPIEGELMAN, BM
影响因子：
6
作者：
Yang, JW;Dai, CS;Liu, YH
通讯作者：
Liu, YH
DOI：
10.1097/01.asn.0000139479.09658.ee
发表时间：
2004-10-01
影响因子：
13.6
作者：
Dai, CS;Yang, JW;Liu, YH
通讯作者：
Liu, YH