Polyol effects on growth factors and MAPK signaling in rat retinal capillary cells.
Polyol effects on growth factors and MAPK signaling in rat retinal capillary cells.
复制标题
多元醇对大鼠视网膜毛细血管细胞生长因子和 MAPK 信号传导的影响。
DOI：
10.1089/jop.2013.0170
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kador,PeterF
中科院分区：
文献类型：
--
作者：
Zhang,Peng;Zhang,Zifeng;Kador,PeterF
目的：最近的研究报告称，大鼠晶状体中的生长因子和信号传导变化并非直接由糖尿病的存在或山梨醇/半乳糖醇（多元醇）的形成/积累引起，而是由与醛糖还原酶（AR）催化的多元醇形成相关的二次渗透压变化引起。 AR 也存在于大鼠视网膜周细胞和内皮细胞中；然而，显着的多元醇形成仅发生在周细胞中，并且这似乎与渗透压变化无关。本研究的目的是确定多元醇的形成和 AR 活性是否与大鼠毛细血管细胞中的生长因子和信号变化有类似的联系，尽管明显不存在渗透压。方法：条件永生化大鼠视网膜周细胞 (TR-rPCT) 和内皮细胞 (TR-iBRB) 细胞系在含有 5.5 mM 葡萄糖的 DMEM 中的 1 型胶原包被培养皿上培养。初始培养 24 小时后，将培养基更换为含有 5.5、25 或 50 mM 葡萄糖或半乳糖（含/不含醛糖还原酶抑制剂 (ARIs) AL1576 或托瑞司他）的无血清培养基，培养时间长达 48 小时。使用抗碱性 FGF、IGF-1、TGF-β、P-ERK1/2、P-SAPK/JNK 和 P-Akt 抗体，通过 Western blot 检测生长因子和转导途径。结果：仅在周细胞中观察到山梨醇积累，而半乳糖醇同时存在于周细胞和内皮细胞中。与在 5.5 mM 葡萄糖中培养的周细胞相比，在高葡萄糖中培养的周细胞显示生长因子碱性 FGF、IGF-1、TGF-β 以及 P-Akt、P-ERK1/2 和 P-SAPK/JNK 中信号传导的表达增加，并且这些表达因 ARI 的存在而正常化。使用半乳糖培养基观察到类似的结果。相反，在高葡萄糖培养基中培养的内皮细胞既没有显示生长因子也没有显示信号变化。在半乳糖培养基中，内皮细胞中碱性 FGF、IGF-1、TGF-β、P-ERK1/2 和 P-SAPK/JNK 的表达增加，而 ARI 仅部分降低这些表达。结论：周细胞中生长因子和 MAPK 信号传导的表达与多元醇的存在有关。周细胞很容易积聚被 ARI 抑制的山梨醇/半乳糖醇，其表达变化与在大鼠晶状体中观察到的相似。相反，内皮细胞仅表现出与半乳糖醇积累相关的部分表达变化。
Purpose:Recent studies report that growth factor and signaling changes in rat lenses do not directly result from the presence of diabetes or sorbitol/galactitol (polyol) formation/accumulation, but from secondary osmotic changes associated with the aldose reductase (AR) catalyzed polyol formation. AR is also present in rat retinal pericyte and endothelial cells; however, significant polyol formation only occurs in pericytes and this does not appear to be linked to osmotic changes. The purpose of this study was to determine whether polyol formation and AR activity are similarly linked to growth factor and signaling changes in the rat capillary cells despite the apparent absence of osmotic stress.Methods:Conditionally immortalized rat retinal pericyte (TR-rPCT) and endothelial (TR-iBRB) cell lines were cultured on collagen type 1-coated dishes in the DMEM containing 5.5 mM glucose. After 24 h of initial culture, the medium was replaced with a serum-free medium containing 5.5, 25, or 50 mM glucose or galactose with/without the aldose reductase inhibitors (ARIs) AL1576 or tolrestat for periods of up to 48 h. Growth factors and transduction pathways were measured by Western blots using the antibodies against basic FGF, IGF-1, TGF-β, P-ERK1/2, P-SAPK/JNK, and P-Akt.Results:Sorbitol accumulation was only observed in pericytes, while galactitol was present in both pericytes and endothelial cells. Pericytes cultured in high glucose showed increased expression of the growth factors basic FGF, IGF-1, TGF-β, and signaling in P-Akt, P-ERK1/2, and P-SAPK/JNK compared with those cultured in 5.5 mM glucose and these expressions were normalized by the presence of ARIs. Similar results were observed with galactose media. In contrast, endothelial cells cultured in high glucose media showed neither growth factor or signaling changes. In galactose media, endothelial cells showed increased expression of basic FGF, IGF-1, TGF-β, P-ERK1/2, and P-SAPK/JNK, which were only partially reduced by ARIs.Conclusion:Growth factor and MAPK signaling expression in pericytes are linked to the presence of polyols. Pericytes, which readily accumulate sorbitol/galactitol that is inhibited by ARIs, show expression changes similar to those observed in rat lenses. In contrast, endothelial cells only show partial expression changes that are linked to galactitol accumulation.
登录
查看更多内容
影响因子：
--
作者：
KADOR, PF;AKAGI, Y;KINOSHITA, JH
通讯作者：
KINOSHITA, JH
影响因子：
7.7
作者：
Dagher, Z;Park, YS;Lorenzi, M
通讯作者：
Lorenzi, M
透视中的壁画细胞。
影响因子：
--
作者：
D. Cogan;T. Kuwabara
通讯作者：
T. Kuwabara
狗视网膜毛细血管周细胞和内皮细胞中多元醇的形成和 NADPH 依赖性还原酶。
影响因子：
4.4
作者：
Sato,S;Secchi,EF;Lizak,MJ;Fukase,S;Ohta,N;Murata,M;Tsai,JY;Kador,PF
通讯作者：
Kador,PF
糖尿病和半乳糖血症性白内障。
DOI：
--
发表时间：
1984
期刊：
Ciba Foundation symposium
影响因子：
--
作者：
P. Kador;J. Kinoshita
通讯作者：
J. Kinoshita