Leptin facilitates proliferation of hepatic stellate cells through up-regulation of platelet-derived growth factor receptor
Leptin facilitates proliferation of hepatic stellate cells through up-regulation of platelet-derived growth factor receptor
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DOI：
10.1016/j.bbrc.2004.08.192
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发表时间：
2004-10-22
影响因子：
3.1
通讯作者：
Sato, N
中科院分区：
文献类型：
--
作者：
Lang, T;Ikejima, K;Sato, N
本研究探讨了瘦素对体外培养的肝星状细胞（HSC）增殖的影响。通过将5-溴-2'-脱氧尿苷（BrdU）掺入细胞核中来评估培养3天的大鼠HSC的增殖。如预期的那样，在PDGF-BB（5ng/ml）存在下8小时，BrdU阳性细胞的百分比增加。与瘦素（10 - 100 nM）共孵育以剂量依赖性方式增强BrdU阳性细胞中的这种PDGF依赖性增加。PDGF受体α和β亚基的信使RNA与瘦素孵育6小时后几乎增加了2 - 3倍。此外，预孵育与瘦素6小时增强PDGF诱导的磷酸化p44/42 MAP激酶和磷酸化Akt水平的增加，在剂量依赖性的方式。然而，在相同的条件下，瘦素本身并不增加磷酸-STAT 3和磷酸-p44/42 MAP激酶水平。相反，瘦素在30分钟内增加HSC中的磷酸化Akt水平，表明磷脂酰肌醇3激酶（PI3K）/Akt通路参与瘦素加速HSC增殖的机制。总之，本研究清楚地表明，瘦素增强PDGF依赖的体外HSC增殖反应。(C)2004爱思唯尔公司All rights reserved.
In the present study, we investigated the effect of leptin on proliferation of hepatic stellate cells (HSCs) in vitro. Proliferation of 3-day cultured rat HSCs was assessed by incorporation of 5-bromo-2'-deoxyuridine (BrdU) into the nuclei. The percentages of BrdU-positive cells were increased in the presence of PDGF-BB (5 ng/ml) for 8 h as expected. Co-incubation with leptin (10-100 nM) potentiates this PDGF-dependent increase in BrdU positive cells in a dose-dependent manner. Messenger RNA for PDGF receptor alpha and beta subunits was increased almost 2- to 3-fold by incubation with leptin for 6 h. Further, pre-incubation with leptin for 6 h enhanced PDGF-induced increases in phospho-p44/42 MAP kinase and phospho-Akt levels in a dose-dependent manner. In the same condition, however, leptin per se did not increase phospho-STAT 3 and phospho-p44/42 MAP kinase levels. Instead, leptin increased phospho-Akt levels in HSCs within 30 min, suggesting that the phosphatidylinositol 3 kinase (PI3K)/Akt pathway is involved in the mechanism by which leptin accelerates the proliferation of HSCs. In conclusion, the present study clearly indicated that leptin potentiates PDGF-dependent proliferative responses of HSCs in vitro. (C) 2004 Elsevier Inc. All rights reserved.