Serine-arginine-rich protein kinase-1 inhibition for the treatment of diabetic retinopathy.
Animals
Arginine
Diabetes Mellitus, Experimental
/ complications
Diabetic Retinopathy
/ drug therapy
Humans
Hyperglycemia
Macular Edema
Ophthalmic Solutions
Protein Kinase Inhibitors
/ pharmacology
Protein Serine-Threonine Kinases
Rats
Serine
Serine-Arginine Splicing Factors
Vascular Endothelial Growth Factor A
/ metabolism
VEGF
diabetic retinopathy
endothelium
splicing
vascular permeability
Journal
American journal of physiology. Heart and circulatory physiology
ISSN: 1522-1539
Titre abrégé: Am J Physiol Heart Circ Physiol
Pays: United States
ID NLM: 100901228
Informations de publication
Date de publication:
01 06 2022
01 06 2022
Historique:
pubmed:
19
3
2022
medline:
14
5
2022
entrez:
18
3
2022
Statut:
ppublish
Résumé
Angiogenic VEGF isoforms are upregulated in diabetic retinopathy (DR), driving pathological growth and fluid leakage. Serine-arginine-rich protein kinase-1 (SRPK1) regulates VEGF splicing, and its inhibition blocks angiogenesis. We tested the hypothesis that SRPK1 is activated in diabetes, and an SRPK1 inhibitor (SPHINX31) switches VEGF splicing in DR and prevents increased vascular permeability into the retina. SRPK1 was activated by high glucose (HG), in a PKC-dependent manner, and was blocked by SPHINX31. HG induced release of SRSF1 from the nuclear speckles, which was also SRPK1 dependent, and increased retinal pigment epithelial (RPE) monolayer admittance, which was reversed by SRPK1 inhibition (
Identifiants
pubmed: 35302878
doi: 10.1152/ajpheart.00001.2022
pmc: PMC9109797
doi:
Substances chimiques
Ophthalmic Solutions
0
Protein Kinase Inhibitors
0
SRSF1 protein, human
0
Vascular Endothelial Growth Factor A
0
Serine-Arginine Splicing Factors
170974-22-8
Serine
452VLY9402
Arginine
94ZLA3W45F
SRPK1 protein, human
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
H1014-H1027Subventions
Organisme : Medical Research Council
ID : MR/L01985X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P003214/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/13/47/30337
Pays : United Kingdom
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