Limits...
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.

Show MeSH

Related in: MedlinePlus

Irisin mediates proliferation via the ERK pathway.HUVECs were treated with or without irisin (20 nM) at indicated time points. (A) Phospho- and total ERK, p38 and AKT levels in cell lysates were analyzed by Western blot. (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 controls and normalized against the untreated control. The data were expressed as the mean ± SE of three independent experiments,**p<0.01 vs. untreated.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4206299&req=5

pone-0110273-g003: Irisin mediates proliferation via the ERK pathway.HUVECs were treated with or without irisin (20 nM) at indicated time points. (A) Phospho- and total ERK, p38 and AKT levels in cell lysates were analyzed by Western blot. (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 controls and normalized against the untreated control. The data were expressed as the mean ± SE of three independent experiments,**p<0.01 vs. untreated.

Mentions: To gain further insights into the relationship between irisin and HUVEC proliferation, the protein levels of ERK, p38 MAPK, and AKT signaling molecules, which are critically involved in cell proliferation, were investigated. As demonstrated in Figure 3, after irisin treatment of HUVECs, phosphorylated ERK (P-ERK) levels were significantly increased at 5 minutes, peaked between 5 and 10 minutes, and decreased at 20 minutes (Fig. 3A). The increase was statistically significant, as quantified by densitometry (Fig. 3B). However, treating HUVECs with irisin had no effect on the level of phospho-p38 and AKT, indicating that the p38 and AKT signaling pathways are not involved in irisin-mediated cell proliferation (Fig. 3A 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 proliferation via the ERK pathway.HUVECs were treated with or without irisin (20 nM) at indicated time points. (A) Phospho- and total ERK, p38 and AKT levels in cell lysates were analyzed by Western blot. (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 controls and normalized against the untreated control. The data were expressed as the mean ± SE of three independent experiments,**p<0.01 vs. untreated.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0110273-g003: Irisin mediates proliferation via the ERK pathway.HUVECs were treated with or without irisin (20 nM) at indicated time points. (A) Phospho- and total ERK, p38 and AKT levels in cell lysates were analyzed by Western blot. (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 controls and normalized against the untreated control. The data were expressed as the mean ± SE of three independent experiments,**p<0.01 vs. untreated.
Mentions: To gain further insights into the relationship between irisin and HUVEC proliferation, the protein levels of ERK, p38 MAPK, and AKT signaling molecules, which are critically involved in cell proliferation, were investigated. As demonstrated in Figure 3, after irisin treatment of HUVECs, phosphorylated ERK (P-ERK) levels were significantly increased at 5 minutes, peaked between 5 and 10 minutes, and decreased at 20 minutes (Fig. 3A). The increase was statistically significant, as quantified by densitometry (Fig. 3B). However, treating HUVECs with irisin had no effect on the level of phospho-p38 and AKT, indicating that the p38 and AKT signaling pathways are not involved in irisin-mediated cell proliferation (Fig. 3A 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