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Irisin promotes human umbilical vein endothelial cell proliferation through the ERK signaling pathway and partly suppresses high glucose-induced apoptosis.

Song H, Wu F, Zhang Y, Zhang Y, Wang F, Jiang M, Wang Z, Zhang M, Li S, Yang L, Wang XL, Cui T, Tang D - PLoS ONE (2014)

Bottom Line: Inhibition of ERK signaling with U0126 decreased the pro-proliferation effect of irisin on HUVECs.It was also demonstrated that irisin reduced high glucose-induced apoptosis by up-regulating Bcl-2 expression and down-regulating Bax, Caspase-9 and Caspase-3 expression.In summary, these results suggested that irisin plays a novel role in sustaining endothelial homeostasis by promoting HUVEC proliferation via the ERK signaling pathway and protects the cell from high glucose-induced apoptosis by regulating Bcl-2,Bax and Caspase expression.

View Article: PubMed Central - PubMed

Affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, P.R.China; Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan, P.R.China; Center for Reproductive Medicine, Zibo Maternal and Child health hospital, Zibo, P.R.China.

ABSTRACT
Irisin is a newly discovered myokine that links exercise with metabolic homeostasis. It is involved in modest weight loss and improves glucose intolerance. However, the direct effects and mechanisms of irisin on vascular endothelial cells (ECs) are not fully understood. In the current study, we demonstrated that irisin promoted Human Umbilical Vein Endothelial Cell (HUVEC) proliferation. It was further demonstrated that this pro-proliferation effect was mediated by irisin-induced activation of extracellular signal-related kinase (ERK) signaling pathways. Inhibition of ERK signaling with U0126 decreased the pro-proliferation effect of irisin on HUVECs. It was also demonstrated that irisin reduced high glucose-induced apoptosis by up-regulating Bcl-2 expression and down-regulating Bax, Caspase-9 and Caspase-3 expression. In summary, these results suggested that irisin plays a novel role in sustaining endothelial homeostasis by promoting HUVEC proliferation via the ERK signaling pathway and protects the cell from high glucose-induced apoptosis by regulating Bcl-2,Bax and Caspase expression.

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ERK inhibitor attenuated the irisin-induced HUVEC proliferation.HUVECs were pretreated with the ERK inhibitor U0126 for 30 min followed by irisin treatment. (A) Western blots analyzed phosphorylated and total ERK proteinexpression. (B) Densitometric analysis of the related bands was expressed as the relative optical band density, which was corrected using respective total proteins as a loading control and normalized against the untreated control. The data were expressed as the mean ± SE of three independent experiments,**p<0.01 vs. untreated group. The effect of the ERK inhibitor on irisin-induced HUVECproliferation was analyzed by Ki67 staining (C, D) and [3H] thymidine uptake (E). The data were expressed as the mean ± SE of three independent experiments, **p<0.01 vs. the irisin-treated group.
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pone-0110273-g004: ERK inhibitor attenuated the irisin-induced HUVEC proliferation.HUVECs were pretreated with the ERK inhibitor U0126 for 30 min followed by irisin treatment. (A) Western blots analyzed phosphorylated and total ERK proteinexpression. (B) Densitometric analysis of the related bands was expressed as the relative optical band density, which was corrected using respective total proteins as a loading control and normalized against the untreated control. The data were expressed as the mean ± SE of three independent experiments,**p<0.01 vs. untreated group. The effect of the ERK inhibitor on irisin-induced HUVECproliferation was analyzed by Ki67 staining (C, D) and [3H] thymidine uptake (E). The data were expressed as the mean ± SE of three independent experiments, **p<0.01 vs. the irisin-treated group.

Mentions: To further examine that irsin enhances HUVEC proliferation through the ERK signaling pathway, U0126 (ERK inhibitor) was used to block ERK activation. Western blot results demonstrated that the irisin-induced ERK phosphorylation was significantly suppressed, while there was no reduction in the amount of total ERK protein (Fig. 4A and B). The irisin-stimulated HUVEC proliferation was evaluated by measuring Ki67 staining in each group (Fig. 4C and D) and [3H] thymidine uptake (Fig. 4E). The data demonstrated that the r-irsin-induced increase of [3H] thymidine uptake was significantly reduced by U0126 treatment. Similar results were observed using immunofluorescent staining, which also demonstrated that blocking ERK activation mitigated irisin-mediated proliferation.


Irisin promotes human umbilical vein endothelial cell proliferation through the ERK signaling pathway and partly suppresses high glucose-induced apoptosis.

Song H, Wu F, Zhang Y, Zhang Y, Wang F, Jiang M, Wang Z, Zhang M, Li S, Yang L, Wang XL, Cui T, Tang D - PLoS ONE (2014)

ERK inhibitor attenuated the irisin-induced HUVEC proliferation.HUVECs were pretreated with the ERK inhibitor U0126 for 30 min followed by irisin treatment. (A) Western blots analyzed phosphorylated and total ERK proteinexpression. (B) Densitometric analysis of the related bands was expressed as the relative optical band density, which was corrected using respective total proteins as a loading control and normalized against the untreated control. The data were expressed as the mean ± SE of three independent experiments,**p<0.01 vs. untreated group. The effect of the ERK inhibitor on irisin-induced HUVECproliferation was analyzed by Ki67 staining (C, D) and [3H] thymidine uptake (E). The data were expressed as the mean ± SE of three independent experiments, **p<0.01 vs. the irisin-treated group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4206299&req=5

pone-0110273-g004: ERK inhibitor attenuated the irisin-induced HUVEC proliferation.HUVECs were pretreated with the ERK inhibitor U0126 for 30 min followed by irisin treatment. (A) Western blots analyzed phosphorylated and total ERK proteinexpression. (B) Densitometric analysis of the related bands was expressed as the relative optical band density, which was corrected using respective total proteins as a loading control and normalized against the untreated control. The data were expressed as the mean ± SE of three independent experiments,**p<0.01 vs. untreated group. The effect of the ERK inhibitor on irisin-induced HUVECproliferation was analyzed by Ki67 staining (C, D) and [3H] thymidine uptake (E). The data were expressed as the mean ± SE of three independent experiments, **p<0.01 vs. the irisin-treated group.
Mentions: To further examine that irsin enhances HUVEC proliferation through the ERK signaling pathway, U0126 (ERK inhibitor) was used to block ERK activation. Western blot results demonstrated that the irisin-induced ERK phosphorylation was significantly suppressed, while there was no reduction in the amount of total ERK protein (Fig. 4A and B). The irisin-stimulated HUVEC proliferation was evaluated by measuring Ki67 staining in each group (Fig. 4C and D) and [3H] thymidine uptake (Fig. 4E). The data demonstrated that the r-irsin-induced increase of [3H] thymidine uptake was significantly reduced by U0126 treatment. Similar results were observed using immunofluorescent staining, which also demonstrated that blocking ERK activation mitigated irisin-mediated proliferation.

Bottom Line: Inhibition of ERK signaling with U0126 decreased the pro-proliferation effect of irisin on HUVECs.It was also demonstrated that irisin reduced high glucose-induced apoptosis by up-regulating Bcl-2 expression and down-regulating Bax, Caspase-9 and Caspase-3 expression.In summary, these results suggested that irisin plays a novel role in sustaining endothelial homeostasis by promoting HUVEC proliferation via the ERK signaling pathway and protects the cell from high glucose-induced apoptosis by regulating Bcl-2,Bax and Caspase expression.

View Article: PubMed Central - PubMed

Affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, P.R.China; Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan, P.R.China; Center for Reproductive Medicine, Zibo Maternal and Child health hospital, Zibo, P.R.China.

ABSTRACT
Irisin is a newly discovered myokine that links exercise with metabolic homeostasis. It is involved in modest weight loss and improves glucose intolerance. However, the direct effects and mechanisms of irisin on vascular endothelial cells (ECs) are not fully understood. In the current study, we demonstrated that irisin promoted Human Umbilical Vein Endothelial Cell (HUVEC) proliferation. It was further demonstrated that this pro-proliferation effect was mediated by irisin-induced activation of extracellular signal-related kinase (ERK) signaling pathways. Inhibition of ERK signaling with U0126 decreased the pro-proliferation effect of irisin on HUVECs. It was also demonstrated that irisin reduced high glucose-induced apoptosis by up-regulating Bcl-2 expression and down-regulating Bax, Caspase-9 and Caspase-3 expression. In summary, these results suggested that irisin plays a novel role in sustaining endothelial homeostasis by promoting HUVEC proliferation via the ERK signaling pathway and protects the cell from high glucose-induced apoptosis by regulating Bcl-2,Bax and Caspase expression.

Show MeSH
Related in: MedlinePlus