PMID- 29228585
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 57
DP  - 2017 Nov 14
TI  - Role of the JAK2/STAT3 signaling pathway in the pathogenesis of type 2 diabetes 
      mellitus with macrovascular complications.
PG  - 96958-96969
LID - 10.18632/oncotarget.18555 [doi]
AB  - 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-1beta 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-1beta in the DV 
      and T2DM groups were higher than those in the control group, and treatment with 
      AG490 decreased the IL-1beta concentration. The JAK2/STAT3/SOCS axis contributes to 
      the development of DV by mediating inflammation associated with vascular 
      endothelial cells and/or monocytes.
FAU - Yang, Mengxue
AU  - Yang M
AD  - Department of Endocrinology, Affiliated Hospital of Zunyi Medical College, Zunyi 
      563000, China.
FAU - Tian, Mei
AU  - Tian M
AD  - Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi 
      563000, China.
FAU - Zhang, Xuan
AU  - Zhang X
AD  - Department of Endocrinology, Affiliated Hospital of Zunyi Medical College, Zunyi 
      563000, China.
FAU - Xu, Jie
AU  - Xu J
AD  - School of Public Health, Zunyi Medical College, Zunyi 563000, China.
FAU - Yang, Bo
AU  - Yang B
AD  - Department of Endocrinology, Affiliated Hospital of Zunyi Medical College, Zunyi 
      563000, China.
FAU - Yu, Jie
AU  - Yu J
AD  - School of Public Health, Zunyi Medical College, Zunyi 563000, China.
FAU - Li, Fengping
AU  - Li F
AD  - Department of Endocrinology, Affiliated Hospital of Zunyi Medical College, Zunyi 
      563000, China.
FAU - Li, Ya
AU  - Li Y
AD  - Department of Endocrinology, Affiliated Hospital of Zunyi Medical College, Zunyi 
      563000, China.
FAU - Li, Sicheng
AU  - Li S
AD  - Department of Endocrinology, Affiliated Hospital of Zunyi Medical College, Zunyi 
      563000, China.
FAU - Li, Xianwen
AU  - Li X
AD  - Department of Endocrinology, Affiliated Hospital of Zunyi Medical College, Zunyi 
      563000, China.
LA  - eng
PT  - Journal Article
DEP - 20170616
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5722537
OTO - NOTNLM
OT  - AG490
OT  - JAK2/STAT3/SOCS signaling pathway
OT  - SOCS
OT  - macrovascular complications
OT  - type 2 diabetes mellitus
COIS- CONFLICTS OF INTEREST The authors do not have any conflicts of interest.
EDAT- 2017/12/13 06:00
MHDA- 2017/12/13 06:01
PMCR- 2017/11/14
CRDT- 2017/12/13 06:00
PHST- 2017/03/04 00:00 [received]
PHST- 2017/06/04 00:00 [accepted]
PHST- 2017/12/13 06:00 [entrez]
PHST- 2017/12/13 06:00 [pubmed]
PHST- 2017/12/13 06:01 [medline]
PHST- 2017/11/14 00:00 [pmc-release]
AID - 18555 [pii]
AID - 10.18632/oncotarget.18555 [doi]
PST - epublish
SO  - Oncotarget. 2017 Jun 16;8(57):96958-96969. doi: 10.18632/oncotarget.18555. 
      eCollection 2017 Nov 14.