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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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Irisin mediates Bax,Bcl-2,GSK-3β, Caspase-9 and Caspase-3 protein levels in HUVECs.HUVECs were cultured with or without irisin (20 nM) for 24 h. Bax, Bcl-2, Bad, GSK-3β, Caspase-9 and Caspase-3 in cell lysates were analyzed by Western blot. (B) Densitometric analysis of the related bands was expressed as the relative optical band density and was corrected using respective total proteins as loading controls and normalized against the untreated control. The data were expressed as the mean ± SE of three independent experiments, *p<0.05 vs. the high glucose-treated group.
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pone-0110273-g006: Irisin mediates Bax,Bcl-2,GSK-3β, Caspase-9 and Caspase-3 protein levels in HUVECs.HUVECs were cultured with or without irisin (20 nM) for 24 h. Bax, Bcl-2, Bad, GSK-3β, Caspase-9 and Caspase-3 in cell lysates were analyzed by Western blot. (B) Densitometric analysis of the related bands was expressed as the relative optical band density and was corrected using respective total proteins as loading controls and normalized against the untreated control. The data were expressed as the mean ± SE of three independent experiments, *p<0.05 vs. the high glucose-treated group.

Mentions: To further investigate the potential mechanism of irisin on high glucose-induced HUVEC apoptosis, the impact of irisin on expression of Bcl-2, Bax, Bad, GSK-3β,Caspase-9 and Caspase-3, several key apoptosis regulator proteins, was examined [12], [13]. The Western blot results indicated that following the treatment with 20 nM irisin, expression of protein Bax, Caspase-9 and Caspase-3 decreased and the anti-apoptotic protein Bcl-2 increased. The expression of GSK-3β and Bad were not influenced. (Fig. 6A and B).


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)

Irisin mediates Bax,Bcl-2,GSK-3β, Caspase-9 and Caspase-3 protein levels in HUVECs.HUVECs were cultured with or without irisin (20 nM) for 24 h. Bax, Bcl-2, Bad, GSK-3β, Caspase-9 and Caspase-3 in cell lysates were analyzed by Western blot. (B) Densitometric analysis of the related bands was expressed as the relative optical band density and was corrected using respective total proteins as loading controls and normalized against the untreated control. The data were expressed as the mean ± SE of three independent experiments, *p<0.05 vs. the high glucose-treated group.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0110273-g006: Irisin mediates Bax,Bcl-2,GSK-3β, Caspase-9 and Caspase-3 protein levels in HUVECs.HUVECs were cultured with or without irisin (20 nM) for 24 h. Bax, Bcl-2, Bad, GSK-3β, Caspase-9 and Caspase-3 in cell lysates were analyzed by Western blot. (B) Densitometric analysis of the related bands was expressed as the relative optical band density and was corrected using respective total proteins as loading controls and normalized against the untreated control. The data were expressed as the mean ± SE of three independent experiments, *p<0.05 vs. the high glucose-treated group.
Mentions: To further investigate the potential mechanism of irisin on high glucose-induced HUVEC apoptosis, the impact of irisin on expression of Bcl-2, Bax, Bad, GSK-3β,Caspase-9 and Caspase-3, several key apoptosis regulator proteins, was examined [12], [13]. The Western blot results indicated that following the treatment with 20 nM irisin, expression of protein Bax, Caspase-9 and Caspase-3 decreased and the anti-apoptotic protein Bcl-2 increased. The expression of GSK-3β and Bad were not influenced. (Fig. 6A and B).

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