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Horm Metab Res 2023; 55(02): 124-135
DOI: 10.1055/a-1939-7355
Original Article: Endocrine Research

Adipocyte-Derived Exosomal LINC00968 Promotes Mouse Retina Microvascular Endothelial Cell Dysfunction in a High-Glucose Environment by Modulating the miR-361–5p/TRAF3 Axis

Wenjing He
1   Department of Endocrinology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
,
Anhua Lin
1   Department of Endocrinology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
,
Chenxiu Wang
1   Department of Endocrinology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
› Author Affiliations Funding This research was supported by Natural Science Foundation of Jiangxi Province (20203BBGL73182 and 20192ACB20029).
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Abstract

As a major cause of mortality, cardiovascular disease is associated with obesity and diabetes. However, the molecular mechanism by which diabetes-obesity causes cardiovascular complications is largely unknown. In this study, the crosstalk mediated by 3T3-L1 preadipocytes and mouse retina microvascular endothelial cells (mRMECs) was determined after co-culturing performed with a Transwell system or measuring exosome uptake by mRMECs. CCK-8 assays, EdU incorporation assays, TUNEL staining, and ELISAs were used to evaluate the functions of mRMECs. Related protein markers were analyzed by western blotting. Our results showed that LINC00968 levels were significantly elevated in the exosomes derived from H-Glu-induced 3T3-L1 preadipocytes. Both H-Glu treatment and co-culture with 3T3-L1 cells damaged mRMECs, as indicated by lower rates of proliferation and higher rates of apoptosis and cell adhesion molecule expression, as well as by induced inflammation and oxidative stress, which were enhanced by combined H-Glu and co-culture treatment. Furthermore, H-Glu and co-culture treatment increased LINC00968 expression in mRMECs, and the exosomes collected from 3T3-L1 cells had a similar effect. Functionally, LINC00968 inhibition protected mRMECs against the effects of H-Glu and co-culture treatment, while LINC00968 played the opposite role. LINC00968 was found to target miR-361–5p, and TRAF3 was identified as a target gene of miR-361–5p. Finally, miR-361–5p overexpression alleviated the effects of LINC00968 on H-Glu-induced mRMEC dysfunction in vitro. In conclusion, our results indicated that in an H-glu environment, adipocyte exosomes damage microvascular endothelial cells via a LINC00968/miR-361–5p/TRAF3 signaling pathway, which could possibly serve as a target for treating diabetes-obesity-triggered microvascular complications.

Key words

3T3-L1 preadipocytes - exosomes - microvascular endothelial cell injury - LINC00968 - diabetes

Supplementary Material



Publication History

Received: 28 July 2022

Accepted after revision: 01 September 2022

Article published online:
10 October 2022

© 2022. Thieme. All rights reserved.

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