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Secretogranin III: a diabetic retinopathy-selective angiogenic factor

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Abstract

Secretogranin III (Scg3) is a member of the granin protein family that regulates the biogenesis of secretory granules. Scg3 was recently discovered as an angiogenic factor, expanding its functional role to extrinsic regulation. Unlike many other known angiogenic factors, the pro-angiogenic actions of Scg3 are restricted to pathological conditions. Among thousands of quantified endothelial ligands, Scg3 has the highest binding activity ratio to diabetic vs. healthy mouse retinas and lowest background binding to normal vessels. In contrast, vascular endothelial growth factor binds to and stimulates angiogenesis of both diabetic and control vasculature. Consistent with its role in pathological angiogenesis, Scg3-neutralizing antibodies alleviate retinal vascular leakage in mouse models of diabetic retinopathy and retinal neovascularization in oxygen-induced retinopathy mice. This review summarizes our current knowledge of Scg3 as a regulatory protein of secretory granules, highlights its new role as a highly disease-selective angiogenic factor, and envisions Scg3 inhibitors as “selective angiogenesis blockers” for targeted therapy.

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Abbreviations

CgA:

Chromogranin A

CCR3:

C-C chemokine receptor type 3

CPE:

Carboxypeptidase E

CNV:

Choroidal neovascularization

DCG:

Dense core secretory granule

DR:

Diabetic retinopathy

HRP-3:

Hepatoma-derived growth factor-related protein 3

mAb:

Monoclonal antibody

OIR:

Oxygen-induced retinopathy

OPD:

Open reading frame

NGS:

Next-generation DNA sequencing

PDR:

Proliferative diabetic retinopathy

RNV:

Retinal neovascularization

ROP:

Retinopathy of prematurity

ROS:

Reactive oxygen species

Scg3:

Secretogranin III

TGN:

Trans-Golgi network

VEGF:

Vascular endothelial growth factor

VEGFR:

VEGF receptor

VGF:

Nerve growth factor inducible protein

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Acknowledgements

This work was supported by National Institutes of Health (NIH) R21EY027065 (WL), NIH Center Core Grant P30-EY014801, and an RPB unrestricted grant.

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Authors and Affiliations

  1. Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, FL, 33136, USA

    Wei Li

  2. Vascular Biology Institute, University of Miami School of Medicine, Miami, FL, 33136, USA

    Wei Li & Keith A. Webster

  3. Department Pharmacology, University of Miami School of Medicine, Miami, FL, 33136, USA

    Keith A. Webster

  4. Schepens Eye Research Institute, Harvard Medical School, Boston, MA, 02114, USA

    Michelle E. LeBlanc

  5. Everglades Biopharma, Miami, FL, 33156, USA

    Hong Tian

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  1. Wei Li
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Correspondence to Wei Li.

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Li, W., Webster, K.A., LeBlanc, M.E. et al. Secretogranin III: a diabetic retinopathy-selective angiogenic factor. Cell. Mol. Life Sci. 75, 635–647 (2018). https://doi.org/10.1007/s00018-017-2635-5

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