PDGF receptors are activated in human epiretinal membranes.
PDGF receptors are activated in human epiretinal membranes.
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DOI：
10.1016/j.exer.2008.10.020
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发表时间：
2009-03
影响因子：
3.4
通讯作者：
Kazauskas, Andrius
中科院分区：
文献类型：
--
作者：
Cui, Jing;Lei, Hetian;Samad, Arif;Basavanthappa, Sreenivasa;Maberley, David;Matsubara, Joanne;Kazauskas, Andrius
先前的研究者报道了从增殖性玻璃体视网膜病变（PVR）患者分离的视网膜前膜表达多种血小板衍生生长因子（PDGF）家族成员和PDGF受体（pdgfr）。配体和受体的共表达增加了自分泌环的可能性，这在PVR的发病机制中可能是重要的。为了开始解决这个问题，我们确定从PVR患者供体分离的视网膜前膜中的PDGFRs是否被激活。事实上，免疫组织化学染色（使用泛型和磷酸化PDGFR抗体）显示两个PDGFR亚基都被激活。这些数据的量化表明，与β亚基相比，表达PDGFR α亚基的细胞比例更高（44 +/ - 13%对32 +/ - 6.5%）。磷酸化PDGFR抗体染色表明，36 +/−10%的PDGFR α亚基被激活，而只有16 +/−5.5%的PDGFR β亚基被激活。因此，激活PDGFR α亚基的百分比增加了2.25倍。诊断细胞型抗体共染色显示视网膜色素上皮细胞和胶质细胞均表达活化的PDGFR α亚基。这些发现支持了最近的发现，即PDGF-C是主要的玻璃体亚型，因为PDGF-C激活PDGFR α亚基的可能性是PDGFR β亚基的3倍。我们得出结论，PDGFR在PVR患者的视网膜前膜中被激活，并且活性PDGFR亚基的谱在功能上支持PDGF- c是PVR患者玻璃体中主要的PDGF异构体的观点。这些发现确定PDGF- a， -AB和C是PDGF家族中最好的治疗靶点。
Previous investigators reported that epiretinal membranes isolated from patients with proliferative vitreoretinopathy (PVR) express various platelet-derived growth factor (PDGF) family members and PDGF receptors (PDGFRs). Co-expression of ligand and receptor raises the possibility of an autocrine loop, which could be of importance in the pathogenesis of PVR. To begin to address this issue we determined whether the PDGFRs in epiretinal membranes isolated from PVR patient donors were activated. Indeed, immunohistochemical staining (using pan- and phospho-PDGFR antibodies) revealed that both PDGFR subunits were activated. Quantification of these data demonstrated that a greater percentage of cells expressed the PDGFR α subunit as compared with the β subunit (44 +/− 13% versus 32 +/− 6.5%). Staining with phospho-PDGFR antibodies indicated that 36 +/−10% of the PDGFR α subunits were activated, whereas only 16 +/− 5.5% of the PDGFR β subunits were activated. Thus, a 2.25 fold greater percentage of the PDGFR α subunits were activated. Co-staining with diagnostic cell-type antibodies indicated that both retinal pigment epithelial and glial cells expressed activated PDGFR α subunits. These findings support the recent discovery that PDGF-C is the major vitreal isoform because PDGF-C is 3 times more likely to activate a PDGFR α subunit as compared with a PDGFR β subunit. We conclude that PDGFRs are activated in epiretinal membranes of patients with PVR, and that the profile of active PDGFR subunits functionally supports the idea that PDGF-C is the predominant PDGF isoform present in the vitreous of patients with PVR. These findings identify PDGF-A, -AB and C as the best therapeutic targets within the PDGF family.
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影响因子：
21.3
作者：
Bergsten, E;Uutela, M;Eriksson, U
通讯作者：
Eriksson, U
影响因子：
4.1
作者：
Cassidy, L;Barry, P;Kennedy, S
通讯作者：
Kennedy, S
影响因子：
4.8
作者：
Reigstad, LJ;Sande, HM;Lillehaug, JR
通讯作者：
Lillehaug, JR
影响因子：
4.1
作者：
Chen, YS;Hackett, SF;Campochiaro, PA
通讯作者：
Campochiaro, PA
影响因子：
2
作者：
ELNER, SG;ELNER, VM;STRIETER, RM
通讯作者：
STRIETER, RM