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Published on: February 25, 2016
Fibroblast growth factor 21 protects against high glucose induced cellular damage and dysfunction of endothelial
Xiao-Mei Wang1, Shuang-Shuang Song, Hang Xiao
1Department of Geriatrics, Southwest Hospital, Third Military Medical University, Chongqing, China.
Aims:
Fibroblast growth factor 21 (FGF21) is a powerful endocrine hormone modulating glucose and lipid metabolism and represents a promising drug for type 2 diabetes. The present study was to determine the effect of FGF21 on high glucose-induced damage and dysfunction in endothelial cells.
Methods:
The protein expression of β-klotho was examined in human umbilical vein endothelial cell (HUVECs) using immunofluorescence and Western blotting. HUVECs were cultured in medium with normal glucose (NG), high glucose (HG) and HG + FGF21 (30 nM). Cell viability, migration, reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase, nitric oxide (NO) production, intracellular cyclic guanosine monophosphate (cGMP) and endothelial nitric oxide synthase (eNOS) phosphorylation at Ser-1177/Ser-633 sites were measured.
Results:
β-klotho, the anchor protein of FGF21, is expressed in HUVECs. Administration of FGF21 prevented HG-induced impairment of cell viability, migration, oxidant stress, NO production and intracellular cGMP levels in HUVECs. FGF21 also rescued HG-induced decrease of eNOS phosphorylation at Ser-1177 and Ser-633. HG and FGF21 had no effects on eNOS phosphorylation at Ser-617 and Thr-495. Inhibition of AMP-activated protein kinase (AMPK), but not Akt or Ca(2+)/calmodulin-dependent protein kinase II, abolished the protective effect of FGF21 on eNOS phosphorylation at Ser-1177. The protective effect of FGF21 on eNOS phosphorylation at Ser-633 was also abolished by inhibition of AMPK but not by Akt or cAMP-dependent protein kinase A.
Conclusion:
Our results provide the first evidence that FGF21 protects against high glucose induced cell damage and eNOS dysfunction in an AMPK-dependent manner in HUVECs, and suggest that FGF21 may be a promoting therapeutic agent for vascular complications in diabetes.
Insights
Fibroblast growth factor 21 (FGF21) protects human endothelial cells from high glucose damage by preserving cell viability and function. This effect is mediated through the AMP-activated protein kinase (AMPK) pathway, suggesting FGF21 as a potential diabetes therapy.
Area of Science:
- Endocrinology
- Cell Biology
- Vascular Biology
Background:
- Fibroblast growth factor 21 (FGF21) is an endocrine hormone crucial for glucose and lipid metabolism.
- FGF21 is a potential therapeutic agent for type 2 diabetes.
- Endothelial cells are vulnerable to high glucose-induced damage in diabetes.
Purpose of the Study:
- To investigate the protective effects of FGF21 on high glucose-induced damage in human umbilical vein endothelial cells (HUVECs).
- To elucidate the molecular mechanisms underlying FGF21's protective action, particularly its impact on endothelial nitric oxide synthase (eNOS) phosphorylation and the involvement of AMP-activated protein kinase (AMPK).
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) were treated with normal glucose (NG), high glucose (HG), or HG + FGF21.
- Assessed cell viability, migration, reactive oxygen species (ROS), nitric oxide (NO) production, and intracellular cyclic guanosine monophosphate (cGMP).
- Examined β-klotho expression, eNOS phosphorylation (Ser-1177/Ser-633), and the role of AMPK, Akt, and protein kinase A (PKA) in FGF21's effects.
Main Results:
- FGF21 treatment prevented high glucose-induced impairment in HUVEC viability, migration, and oxidative stress.
- FGF21 restored high glucose-impaired nitric oxide (NO) production and intracellular cyclic guanosine monophosphate (cGMP) levels.
- FGF21 rescued high glucose-induced decrease in eNOS phosphorylation at Ser-1177 and Ser-633 in an AMPK-dependent manner.
Conclusions:
- FGF21 demonstrates significant protective effects against high glucose-induced endothelial cell damage and eNOS dysfunction.
- The protective mechanisms involve the AMP-activated protein kinase (AMPK) pathway.
- FGF21 holds promise as a therapeutic agent for managing vascular complications associated with diabetes.
