Pigment Epithelium-Derived Factor (PEDF) Receptors Are Involved in Survival of Retinal Neurons.

Pigment Epithelium-Derived Factor (PEDF) Receptors Are Involved in Survival of Retinal Neurons.
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DOI:
10.3390/ijms22010369
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发表时间:
2020-12-31
影响因子:
5.6
通讯作者:
Unterlauft JD
Unterlauft JD
中科院分区:
生物学2区
文献类型:
--
作者:
Bürger S;Meng J;Zwanzig A;Beck M;Pankonin M;Wiedemann P;Eichler W;Unterlauft JD

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视网膜神经节细胞(RGCs)的死亡是青光眼、糖尿病或缺血性视网膜病变等视网膜疾病的特征。色素上皮衍生因子(PEDF)是一种多功能的分泌蛋白,在视网膜中介导神经保护和血管生成的抑制。我们研究了PEDF的两种受体,patatin-like phospholipase 2 gene product/PEDF- r和laminin receptor (LR),在正常氧合和缺氧条件下,在血清饥饿的RGC中表达和调控,并研究了它们与视网膜神经元细胞存活的关系。我们发现PEDF-R和LR在RGC和R28视网膜前体细胞中共表达。这两种受体的表达在视网膜胶质细胞(m<s:1> ller)的复杂分泌物存在时增强,并在缺氧条件下被VEGF上调。PEDF- r和LR敲低的细胞显示抗凋亡Bcl-2家族成员(Bcl-2, Bcl-xL)和神经保护介质(PEDF, VEGF, BDNF)的表达明显减弱,这表明PEDF- r和LR都介导PEDF对RGC的促生存作用。虽然这项研究没有提供证据证明PEDF- r或LR对促进存活的差异影响,但它仍然强调了PEDF受体对视网膜神经元活力的重要性。
The demise of retinal ganglion cells (RGCs) is characteristic of diseases of the retina such as glaucoma and diabetic or ischemic retinopathies. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted protein that mediates neuroprotection and inhibition of angiogenesis in the retina. We have studied expression and regulation of two of several receptors for PEDF, patatin-like phospholipase 2 gene product/PEDF-R and laminin receptor (LR), in serum-starved RGC under normoxia and hypoxia and investigated their involvement in the survival of retinal neuronal cells. We show that PEDF-R and LR are co-expressed in RGC and R28 retinal precursor cells. Expression of both receptors was enhanced in the presence of complex secretions from retinal glial (Müller) cells and upregulated by VEGF and under hypoxic conditions. PEDF-R- and LR-knocked-down cells demonstrated a markedly attenuated expression of anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-xL) and neuroprotective mediators (PEDF, VEGF, BDNF) suggesting that both PEDF-R and LR mediate pro-survival effects of PEDF on RGC. While this study does not provide evidence for a differential survival-promoting influence of either PEDF-R or LR, it nevertheless highlights the importance of both PEDF receptors for the viability of retinal neurons.
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