PMID- 28979671
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 9
IP  - 9
DP  - 2017
TI  - Reduced beta 2 glycoprotein I prevents high glucose-induced cell death in HUVECs 
      through miR-21/PTEN.
PG  - 3935-3949
AB  - High serum beta 2 glycoprotein I (beta2GPI) is associated with complications of type 
      2 diabetes mellitus (DM), and especially microvascular disorders. In contrast, 
      reduced beta2GPI (Rbeta2GPI) can prevent diabetic vascular injury. This study aimed to 
      investigate the protective function of Rbeta2GPI in DM vascular disorders, and to 
      assess the under lying mechanisms. High glucose-induced injury in human umbilical 
      vein endothelial cells (HUVECs) was used to model hyperglycemia. Alow 
      concentration of Rbeta2GPI (0.5 muM), but not beta2GPI, mitigated high glucose-induced 
      cell injury. High glucose decreased miR-21 expression and Akt phosphorylation at 
      6 h, but facilitated their expression at 48 h. Moreover, high glucose decreased 
      phosphatase and tensin homolog deleted on chromosome ten(PTEN) expression at 6 h, 
      but facilitatedits expression at 48 h. Importantly, by promoting miR-21 
      expression, Rbeta2GPI mitigated high glucose-induced PTEN expression, reduced Akt 
      phosphorylation and nitric oxide synthase activity, and increased 
      cyclooxygenase-2 activity and cell loss. Similar to Rbeta2GPI, an miR-21 mimic (1 
      pM) and PTEN inhibition (1 muM bpV, or PTEN silencing) exerted protective action, 
      while an Akt signaling pathway inhibitor (LY294002, 1 muM) aborted the effect of 
      Rbeta2GPI on high glucose-induced cell injury. Finally, Rbeta2GPI inhibited high 
      glucose-induced apoptosis via a mitochondria-dependent pathway. These data reveal 
      that Rbeta2GPI exerts protective action in high glucose-induced HUVEC injury. The 
      mechanism is related to the miR-21-PTEN-Akt pathway and mitochondria-dependent 
      apoptosis. This study provides in vitro data supporting the therapeutic effect of 
      Rbeta2GPI in diabetic vascular injury.
FAU - Zhang, Jing-Yun
AU  - Zhang JY
AD  - Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key 
      Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin 
      Institute of Endocrinology, Tianjin Medical University300070 Tianjin, China.
FAU - Ma, Jun
AU  - Ma J
AD  - Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key 
      Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin 
      Institute of Endocrinology, Tianjin Medical University300070 Tianjin, China.
FAU - Yu, Pei
AU  - Yu P
AD  - Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key 
      Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin 
      Institute of Endocrinology, Tianjin Medical University300070 Tianjin, China.
FAU - Tang, Guang-Jie
AU  - Tang GJ
AD  - Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key 
      Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin 
      Institute of Endocrinology, Tianjin Medical University300070 Tianjin, China.
FAU - Li, Chun-Jun
AU  - Li CJ
AD  - Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key 
      Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin 
      Institute of Endocrinology, Tianjin Medical University300070 Tianjin, China.
FAU - Yu, De-Min
AU  - Yu DM
AD  - Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key 
      Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin 
      Institute of Endocrinology, Tianjin Medical University300070 Tianjin, China.
FAU - Zhang, Qiu-Mei
AU  - Zhang QM
AD  - Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key 
      Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin 
      Institute of Endocrinology, Tianjin Medical University300070 Tianjin, China.
LA  - eng
PT  - Journal Article
DEP - 20170915
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC5622240
OTO - NOTNLM
OT  - HUVECs
OT  - PTEN
OT  - Reduced beta 2 glycoprotein I
OT  - miR-21
OT  - nitric oxide
COIS- None.
EDAT- 2017/10/06 06:00
MHDA- 2017/10/06 06:01
PMCR- 2017/09/15
CRDT- 2017/10/06 06:00
PHST- 2017/02/21 00:00 [received]
PHST- 2017/08/13 00:00 [accepted]
PHST- 2017/10/06 06:00 [entrez]
PHST- 2017/10/06 06:00 [pubmed]
PHST- 2017/10/06 06:01 [medline]
PHST- 2017/09/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2017 Sep 15;9(9):3935-3949. eCollection 2017.