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Oncotarget. 2017 Jun 16;8(57):96958-96969. doi: 10.18632/oncotarget.18555. eCollection 2017 Nov 14.

Role of the JAK2/STAT3 signaling pathway in the pathogenesis of type 2 diabetes mellitus with macrovascular complications.

Author information

1
Department of Endocrinology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
2
Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
3
School of Public Health, Zunyi Medical College, Zunyi 563000, China.

Abstract

This study investigated the role of the JAK2/STAT3/SOCS pathway in type 2 diabetes mellitus (T2DM) and macrovascular complications (DV) (T2DM+DV) conditions. Human umbilical vein endothelial cells (HUVECs) were co-cultured with human monocytes (THP-1) and exposed to peripheral blood sera from 30 T2DM patients, 30 patients with T2DM+DV and 30 healthy controls; the groups were divided into the control, T2DM, DV, T2DM+AG490 and DV+AG490 groups. Chemotaxis of treated HUVECs toward THP-1 cells was assessed using Transwell migration. The mRNA expression of JAK2, STAT3, VEGF and FLT1 was evaluated using RT-PCR, whereas the protein levels of ICAM-1, p-JAK2, JAK2, STAT3, p-STAT3, SOCS1 and SOCS3 were determined using western blotting. p-STAT3 was observed using immunofluorescence. The IL-1β concentrations were assessed by ELISA. AG90 was used as a specific inhibitor of JAK2/STAT3 signaling. The chemotaxis assays revealed a migratory order of DV>DM>control, and AG490 treatment decreased chemotaxis. Additionally, p-STAT3 fluorescence was noticeably increased in the DM group and more so in the DV group. The mRNA expression of JAK2, STAT3, VEGF and FLT1 and the protein levels of ICAM-1, p-JAK2, p-STAT3, SOCS1 and SOCS3 were significantly higher in the T2DM and DV groups than in the control group and in the AG490-treated groups than in the untreated groups. The supernatant concentrations of IL-1β in the DV and T2DM groups were higher than those in the control group, and treatment with AG490 decreased the IL-1β concentration. The JAK2/STAT3/SOCS axis contributes to the development of DV by mediating inflammation associated with vascular endothelial cells and/or monocytes.

KEYWORDS:

AG490; JAK2/STAT3/SOCS signaling pathway; SOCS; macrovascular complications; type 2 diabetes mellitus

Conflict of interest statement

CONFLICTS OF INTEREST The authors do not have any conflicts of interest.

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