血小板源性生长因子受体
蛋白激酶B
细胞生长
化学
MAPK/ERK通路
肝星状细胞
血小板衍生生长因子
生长因子
分子生物学
细胞培养
磷酸化
细胞生物学
生物化学
生物
受体
内分泌学
遗传学
作者
Yoichiro Takami,Hirofumi Uto,Masahiko Takeshita,Kai Hao,Ena Akamatsu,Akihiro Moriuchi,Susumu Hasegawa,Makoto Oketani,Akio Ido,Hiroaki Kataoka,Hirohito Tsubouchi
标识
DOI:10.1111/j.1872-034x.2009.00589.x
摘要
Aim: Hepatic stellate cell (HSC) proliferation plays a pivotal role in liver fibrogenesis, and agents that suppress HSC activation, including platelet‐derived growth factor (PDGF)‐induced HSC proliferation, are good candidates for antifibrogenic therapies. In this report, we use the LI90 HSC line to elucidate the antifibrogenic effects of proanthocyanidin derived from the leaves of Vaccinium virgatum . Methods: Proanthocyanidin (PAC) was extracted from the leaves of blueberry V. virgatum (BB‐PAC), grape seeds (GS‐PAC) and Croton lechleri (CL‐PAC). These extracts were examined for their effects on PDGF‐BB‐induced LI90 cell proliferation and DNA synthesis. Extracellular signal‐regulated kinase (ERK) and Akt phosphorylation and PDGF receptor‐β (PDGFR‐β) expression were evaluated by western blot analysis. Results: BB‐PAC potently suppressed PDGF‐BB‐induced proliferation and DNA synthesis of LI90 cells. BB‐PAC also suppressed PDGF‐BB‐induced DNA synthesis in primary cultured rat HSC. Moreover, GS‐PAC and CL‐PAC suppressed PDGF‐BB‐induced DNA synthesis in LI90 cells. In contrast, the monomeric PAC catechin and epicatechin and dimeric PAC procyanidin B2 only slightly suppressed PDGF‐BB‐induced DNA synthesis. Western blot analysis showed that BB‐PAC completely or partially inhibited PDGF‐BB‐induced ERK and Akt phosphorylation, respectively. In addition, BB‐PAC partially inhibited the PDGF‐BB‐induced degradation of PDGFR‐β. Conclusion: Our results suggest that BB‐PAC suppresses activated HSC by inhibiting the PDGF signaling pathway. In addition, these results provide novel findings that may facilitate the development of antifibrogenic agents.
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