Association of 150‐kDa oxygen‐regulated protein with vascular endothelial growth factor in proliferative diabetic retinopathy

  title={Association of 150‐kDa oxygen‐regulated protein with vascular endothelial growth factor in proliferative diabetic retinopathy},
  author={Ahmed M. Abu El-Asrar and Ajmal Ahmad and Kaiser Alam and Emilie Bittoun and Mohammad Mairaj Siddiquei and Ghulam Mohammad and Ahmed Mousa and Gert De Hertogh and Ghislain Opdenakker},
  journal={Acta Ophthalmologica},
150‐kDa oxygen‐regulated protein (ORP150), a member of heat‐shock protein family located in endoplasmic reticulum (ER), has a critical role in secretion of vascular endothelial growth factor (VEGF). We investigated expression levels of ORP150 and correlated these levels with VEGF and total vitreous antioxidant capacity (TAC) in proliferative diabetic retinopathy (PDR). We also examined expression of ORP150 in retinas of diabetic rats and in human retinal microvascular endothelial cells (HRMEC). 

The Vitreous Ecosystem in Diabetic Retinopathy: Insight into the Patho-Mechanisms of Disease

The molecular patho-mechanisms of diabetic retinopathy based upon current vitreous research are discussed and areas of concentration include: the current level of knowledge of growth factors, cytokine and chemokine mediators, and lipid-derived metabolites in the Vitreous.

Changes in aqueous and vitreous inflammatory cytokine levels in proliferative diabetic retinopathy: a systematic review and meta-analysis

A comprehensive search of the literature without year limitation was conducted to January 18, 2021, which identified 341 studies assessing vitreous or aqueous cytokine levels in PDR, and this extensive list of cytokines speaks to the complexity of PDR pathogenesis and informs future investigations into disease pathogenesis, prognosis, and management.

Pathological Perturbations in Diabetic Retinopathy: Hyperglycemia, AGEs, Oxidative Stress and Inflammatory Pathways.

The role of hyperglycemia, oxidative stress and inflammation in the pathogenesis of DR is discussed, and the cross-talk amongst these pathways is highlighted in an attempt to understand the complex interplay of these mechanisms.

Alterations of Human Plasma Proteome Profile on Adaptation to High-Altitude Hypobaric Hypoxia.

The findings highlight the contributions of complement and coagulation cascades, antioxidative stress, and glycolysis in acclimatization to Hypobaric hypoxia and provide a foundation for developing potential diagnostic or/and therapeutic biomarkers for high altitude hypobarichypoxia-induced diseases.

Recurrent Infections and Immunodeficiency Caused by Severe Pancytopenia Associated with a Novel Life-Threatening Mutation in Hypoxia-Upregulated Protein 1

A novel homozygous pathogenic variant in HYOU1 was identified, causing anemia, thrombocytopenia and severe panleukopenia and immunodeficiency in the second month of age, leading to consistent high-grade fever, regression of brain functions and recurrent infections; ultimately resulting in the patient expiring at three and half months of age.

OTT_A_297332 1727..1735

  • 2021

Biological Function of HYOU1 in Tumors and Other Diseases

The updates in H YOU1 are summarized and the potential therapeutic effects of HYOU1 are discussed, which are a molecular target for therapy of many endoplasmic reticulum-related diseases and a potential therapeutic target for cancer.



Antitumor effect of reduction of 150‐kDa oxygen‐regulated protein expression on human prostate cancer cells

  • T. MiyagiO. Hori M. Namiki
  • Biology, Medicine
    International journal of urology : official journal of the Japanese Urological Association
  • 2002
Whether transduced antisense ORP150 cDNA can reduce angiogenicity and tumorigenicity through suppression of VEGF secretion is examined.

Expression of hypoxia-inducible factor-1α and the protein products of its target genes in diabetic fibrovascular epiretinal membranes

An adverse angiogenic milieu in PDR epiretinal membranes favouring aberrant neovascularisation and endothelial abnormalities is suggested, suggesting an important role in the pathogenesis of PDR.


  • J. L.
  • Medicine
  • 1995
The data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.

Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy

The results suggest the potential importance of IL‐6/STAT3 signaling in regulating endothelial permeability and provide a therapeutic target to prevent the pathology of diabetic retinopathy.

Osteoprotegerin Is a New Regulator of Inflammation and Angiogenesis in Proliferative Diabetic Retinopathy.

Osteoprotegerin potentiated the angiogenic effect of VEGF in the in vivo protein gelatin plug assay and suggest that OPG is involved in PDR angiogenesis.

Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport.

An important role is suggested for ORP150 in the setting of impaired wound repair and a key, inducible chaperone-like molecule in the ER is identified, suggesting a novel facet of the angiogenic response may be amenable to therapeutic manipulation.

Regulation of tumor angiogenesis by oxygen-regulated protein 150, an inducible endoplasmic reticulum chaperone.

A critical role for the inducible ER chaperone ORP150 is demonstrated in tumor-mediated angiogenesis via processing of VEGF, and this work highlights a new facet of angiogenic mechanisms amenable to therapeutic manipulation in tumors.

Mutual enhancement between high-mobility group box-1 and NADPH oxidase-derived reactive oxygen species mediates diabetes-induced upregulation of retinal apoptotic markers

The results of this study suggest that there is a mutual enhancement between HMGB1 and Nox-derived ROS in the diabetic retina, which may promote diabetes-induced upregulation of retinal apoptotic markers.

Positive association of pigment epithelium-derived factor with total antioxidant capacity in the vitreous fluid of patients with proliferative diabetic retinopathy

PEDF levels are associated with total antioxidant capacity of vitreous fluid in humans, and suggests that PEDF may act as an endogenous antioxidant in the eye and could play a protective role against PDR.

Marked, sustained expression of a novel 150-kDa oxygen-regulated stress protein, in severely ischemic mouse neurons.