2010
DOI: 10.1167/iovs.09-3511
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Inhibition of JAK2/STAT3-Mediated VEGF Upregulation under High Glucose Conditions by PEDF through a Mitochondrial ROS Pathway In Vitro

Abstract: For the first time it has been demonstrated that PEDF can decrease mitochondria-derived ROS generation and subsequently downregulate VEGF expression, possibly through inhibiting HG-induced JAK2/STAT3 activation, which may offer a promising strategy for halting the development of complications of diabetes.

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Cited by 49 publications
(31 citation statements)
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“…However, the role of PEDF in regulating the levels and activity of the other major antioxidant enzymes -catalase and Cu/Zn superoxide dismutase (SOD) -has yet to be elucidated. Similarly, JAK2/STAT3 and ERKs (ERK1/2) are activated in bovine retinal capillary ECs (BRECs) (Zheng et al 2010) and human retinal pigment epithelial cells (ARPE-19) respectively . PEDF decreased the level of mitochondria-generated ROS, suppressed JAK2/STAT3 activation, leading to lower VEGF mRNA expression (Zheng et al 2010).…”
Section: Role Of Oxidative Stress and Inflammation In The Developmentmentioning
confidence: 99%
See 1 more Smart Citation
“…However, the role of PEDF in regulating the levels and activity of the other major antioxidant enzymes -catalase and Cu/Zn superoxide dismutase (SOD) -has yet to be elucidated. Similarly, JAK2/STAT3 and ERKs (ERK1/2) are activated in bovine retinal capillary ECs (BRECs) (Zheng et al 2010) and human retinal pigment epithelial cells (ARPE-19) respectively . PEDF decreased the level of mitochondria-generated ROS, suppressed JAK2/STAT3 activation, leading to lower VEGF mRNA expression (Zheng et al 2010).…”
Section: Role Of Oxidative Stress and Inflammation In The Developmentmentioning
confidence: 99%
“…Similarly, JAK2/STAT3 and ERKs (ERK1/2) are activated in bovine retinal capillary ECs (BRECs) (Zheng et al 2010) and human retinal pigment epithelial cells (ARPE-19) respectively . PEDF decreased the level of mitochondria-generated ROS, suppressed JAK2/STAT3 activation, leading to lower VEGF mRNA expression (Zheng et al 2010). On the contrary, PEDF can induce ERK1/2 phosphorylation and activation and protect ARPE-19 cells against H 2 O 2 -mediated oxidative stress .…”
Section: Role Of Oxidative Stress and Inflammation In The Developmentmentioning
confidence: 99%
“…Additionally, high glucose can stimulate STAT3 phosphorylation in retinal endothelial and RPE cells (3840). The activation of STAT3 plays a role in inflammatory pathways and can initiate ER stress under high glucose conditions in TR-iBRB cells (39).…”
Section: Introductionmentioning
confidence: 99%
“…2). A widely reported finding is significantly elevated intracellular and mitochondrial ROS formation and thus excessive oxidative stress, accompanied by the increased expression of UCP2 in endothelial cells exposed to high glucose concentrations [9,27,[39][40][41][42][43]. We have demonstrated that under phosphorylating conditions, the increased UCP activity in the mitochondria isolated from high glucose-exposed endothelial cells leads to a significantly higher reduction in the oxidative phosphorylation yield (ATP synthesis) [27].…”
Section: Uncoupling Protein 2 (Ucp2) and Endothelial (Dys)functionmentioning
confidence: 70%