Robo4-mediated pancreatic endothelial integrity decreases inflammation and islet destruction in autoimmune diabetes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F20%3A43901217" target="_blank" >RIV/60076658:12310/20:43901217 - isvavai.cz</a>

Result on the web

<a href="https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.201900125RR" target="_blank" >https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.201900125RR</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1096/fj.201900125RR" target="_blank" >10.1096/fj.201900125RR</a>

Result language

angličtina

Original language name

Robo4-mediated pancreatic endothelial integrity decreases inflammation and islet destruction in autoimmune diabetes

Original language description

In Type 1 Diabetes Mellitus (T1DM), leukocyte infiltration of the pancreatic islets and the resulting immune-mediated destruction of beta cells precede hyperglycemia and clinical disease symptoms. In this context, the role of the pancreatic endothelium as a barrier for autoimmunity- and inflammation-related destruction of the islets is not well studied. Here, we identified Robo4, expressed on endothelial cells, as a regulator of pancreatic vascular endothelial permeability during autoimmune diabetes. Circulating levels of Robo4 were upregulated in mice subjected to the Multiple Low-Dose Streptozotocin (MLDS) model of diabetes. Upon MLDS induction, Robo4-deficiency resulted in increased pancreatic vascular permeability, leukocyte infiltration to the islets and islet apoptosis, associated with reduced insulin levels and faster diabetes development. On the contrary, in vivo administration of Slit2 in mice modestly delayed the emergence of hyperglycaemia and ameliorated islet inflammation in MLDS-induced diabetes. Thus, Robo4-mediated endothelial barrier integrity reduces insulitis and islet destruction in autoimmune diabetes. Our findings highlight the importance of the endothelium as gatekeeper of pancreatic inflammation during T1DM development and may pave the way for novel Robo4-related therapeutic approaches for autoimmune diabetes.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

FASEB Journal

ISSN

0892-6638

e-ISSN

—

Volume of the periodical

34

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

3336-3346

UT code for WoS article

000506442300001

EID of the result in the Scopus database

2-s2.0-85078677283