TY - JOUR
T1 - Secretogranin III
T2 - a diabetic retinopathy-selective angiogenic factor
AU - Li, Wei
AU - Webster, Keith A.
AU - LeBlanc, Michelle E.
AU - Tian, Hong
N1 - Funding Information:
Acknowledgements This work was supported by National Institutes of Health (NIH) R21EY027065 (WL), NIH Center Core Grant P30-EY014801, and an RPB unrestricted grant.
Funding Information:
This work was supported by National Institutes of Health (NIH) R21EY027065 (WL), NIH Center Core Grant P30-EY014801, and an RPB unrestricted grant.
Publisher Copyright:
© 2017, Springer International Publishing AG.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - Anti-angiogenesis therapy
KW - Comparative ligandomics
KW - Diabetic macular edema
KW - Ligandomics
KW - Proliferative diabetic retinopathy
KW - Retinopathy of prematurity
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U2 - 10.1007/s00018-017-2635-5
DO - 10.1007/s00018-017-2635-5
M3 - Review article
C2 - 28856381
AN - SCOPUS:85045289392
VL - 75
SP - 635
EP - 647
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
SN - 1420-682X
IS - 4
ER -