A cyclopentenone prostaglandin activates mesangial MAP kinase independently of PPARgamma.
A cyclopentenone prostaglandin activates mesangial MAP kinase independently of PPARgamma.
复制标题
DOI：
10.1006/bbrc.2001.4301
复制
发表时间：
2001-02
影响因子：
3.1
通讯作者：
W. Wilmer;C. Dixon;Ling Lu;T. Hilbelink;B. Rovin
中科院分区：
文献类型：
--
作者：
W. Wilmer;C. Dixon;Ling Lu;T. Hilbelink;B. Rovin
有丝分裂原活化蛋白（MAP）激酶介导肾小球系膜细胞对各种生理和病理刺激的反应。本研究探讨环戊酮前列腺素15-脱氧- δ(12,14)-前列腺素J2 （15d-PGJ2）对人肾小球系膜细胞MAP激酶的影响。我们发现15d-PGJ2剂量依赖性地增加了人系膜细胞的细胞外信号调节激酶（ERK）活性，但对jun - nh2末端激酶或p38 MAP激酶没有影响。尽管15d-PGJ2是一种过氧化物酶体增殖物激活受体（PPAR）配体，并且PPAR可通过系膜细胞表达，但噻唑烷二酮类PPAR受体激动剂西格列酮不会激活ERK。此外，合成的PPARgamma拮抗剂不会减弱15d-PGJ2对ERK的激活。然而，15d- pgj2介导的ERK激活被MEK抑制剂PD 098059阻断，似乎需要磷脂酰肌醇-3激酶，但独立于蛋白激酶C的激活。这些结果证明了15d-PGJ2在独立于PPARgamma的情况下诱导人系膜细胞ERK的新作用。
The mitogen-activated protein (MAP) kinases mediate the response of renal glomerular mesangial cells to a variety of physiologic and pathologic stimuli. This investigation examines the effect of the cyclopentenone prostaglandin 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) on MAP kinases in human mesangial cells. We show that 15d-PGJ2 dose-dependently increases the extracellular signal-regulated kinase (ERK) activity of human mesangial cells, but has no effect on Jun-NH2-terminal kinase or p38 MAP kinase. Despite the fact that 15d-PGJ2 is a peroxisome proliferator-activated receptor (PPAR) ligand, and PPARgamma is shown to be expressed by mesangial cells, the thiazolidinedione PPARgamma agonist ciglitazone does not activate ERK. Additionally, a synthetic PPARgamma antagonist does not attenuate the activation of ERK by 15d-PGJ2. 15d-PGJ2-mediated ERK activation is however blocked by the MEK inhibitor PD 098059, appears to require phosphatidylinositol-3 kinase, but is independent of protein kinase C activation. These results demonstrate a novel effect of 15d-PGJ2 to induce ERK in human mesangial cells independently of PPARgamma.