Limits...
Irisin Induces Angiogenesis in Human Umbilical Vein Endothelial Cells In Vitro and in Zebrafish Embryos In Vivo via Activation of the ERK Signaling Pathway.

Wu F, Song H, Zhang Y, Zhang Y, Mu Q, Jiang M, Wang F, Zhang W, Li L, Li H, Wang Y, Zhang M, Li S, Yang L, Meng Y, Tang D - PLoS ONE (2015)

Bottom Line: Although our recent evidence supported the contribution of irisin to vascular endothelial cell (ECs) proliferation and apoptosis, further research of irisin involvement in the angiogenesis of ECs was not conclusive.We also found that irisin activated extracellular signal-related kinase (ERK) signaling pathways.Inhibition of ERK signaling by using U0126 decreased the pro-migration and pro-angiogenic effect of irisin on HUVEC.

View Article: PubMed Central - PubMed

Affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P.R. China.

ABSTRACT
As a link between exercise and metabolism, irisin is assumed to be involved in increased total body energy expenditure, reduced body weight, and increased insulin sensitivity. Although our recent evidence supported the contribution of irisin to vascular endothelial cell (ECs) proliferation and apoptosis, further research of irisin involvement in the angiogenesis of ECs was not conclusive. In the current study, it was found that irisin promoted Human Umbilical Vein Endothelial Cell (HUVEC) angiogenesis via increasing migration and tube formation, and attenuated chemically-induced intersegmental vessel (ISV) angiogenic impairment in transgenic TG (fli1: GFP) zebrafish. It was further demonstrated that expression of matrix metalloproteinase (MMP) 2 and 9 were also up-regulated in endothelial cells. We also found that irisin activated extracellular signal-related kinase (ERK) signaling pathways. Inhibition of ERK signaling by using U0126 decreased the pro-migration and pro-angiogenic effect of irisin on HUVEC. Also, U0126 inhibited the elevated expression of MMP-2 and MMP-9 when they were treated with irisin. In summary, these findings provided direct evidence that irisin may play a pivotal role in maintaining endothelium homeostasis by promoting endothelial cell angiogenesis via the ERK signaling pathway.

No MeSH data available.


Related in: MedlinePlus

Effect of the ERK inhibitor on irisin-induced cell migration of HUVEC.(A) and (C) HUVEC were pretreated with the ERK inhibitor U0126 (10 μM) for 30 min and cultured with or without irisin (20 nM) for 24 h, images of wound-healing assays and Transwell assays were taken at 0 and 24 h. (B) Percent wound closure at 12 and 24 h after scratch is shown (n = 5). (D) The number of cells that migrated to the lower side of the membranes after incubation for 24 h are shown and relative migration was quantified using Image-Pro Plus software (n = 5). Data are mean± SE. ** P< 0.01 vs. irisin-treated group, determined by unpaired two-tailed Student’s t-test.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4524626&req=5

pone.0134662.g005: Effect of the ERK inhibitor on irisin-induced cell migration of HUVEC.(A) and (C) HUVEC were pretreated with the ERK inhibitor U0126 (10 μM) for 30 min and cultured with or without irisin (20 nM) for 24 h, images of wound-healing assays and Transwell assays were taken at 0 and 24 h. (B) Percent wound closure at 12 and 24 h after scratch is shown (n = 5). (D) The number of cells that migrated to the lower side of the membranes after incubation for 24 h are shown and relative migration was quantified using Image-Pro Plus software (n = 5). Data are mean± SE. ** P< 0.01 vs. irisin-treated group, determined by unpaired two-tailed Student’s t-test.

Mentions: We demonstrated that ERK, not p38 MAPK or AKT signaling pathways were involved in irisin-induced HUVEC proliferation and apoptosis [15]. It was confirmed that phosphorylated ERK (P-ERK) was significantly increased after treatment with irisin for 5 min and 10 min (S1A Fig). To explore whether ERK is involved in HUVEC migration and tube formation, a specific inhibitor of the ERK pathway, U0126, was used to block ERK activation. As shown in Figs 5 and 6, irisin-induced cell migration and tube formation was significantly inhibited by 10 μM U0126. Also, Western blot showed that the irisin-induced increase in ERK phosphorylation was inhibited by pre-treatment with U0126 (S1B and S1C Fig).


Irisin Induces Angiogenesis in Human Umbilical Vein Endothelial Cells In Vitro and in Zebrafish Embryos In Vivo via Activation of the ERK Signaling Pathway.

Wu F, Song H, Zhang Y, Zhang Y, Mu Q, Jiang M, Wang F, Zhang W, Li L, Li H, Wang Y, Zhang M, Li S, Yang L, Meng Y, Tang D - PLoS ONE (2015)

Effect of the ERK inhibitor on irisin-induced cell migration of HUVEC.(A) and (C) HUVEC were pretreated with the ERK inhibitor U0126 (10 μM) for 30 min and cultured with or without irisin (20 nM) for 24 h, images of wound-healing assays and Transwell assays were taken at 0 and 24 h. (B) Percent wound closure at 12 and 24 h after scratch is shown (n = 5). (D) The number of cells that migrated to the lower side of the membranes after incubation for 24 h are shown and relative migration was quantified using Image-Pro Plus software (n = 5). Data are mean± SE. ** P< 0.01 vs. irisin-treated group, determined by unpaired two-tailed Student’s t-test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524626&req=5

pone.0134662.g005: Effect of the ERK inhibitor on irisin-induced cell migration of HUVEC.(A) and (C) HUVEC were pretreated with the ERK inhibitor U0126 (10 μM) for 30 min and cultured with or without irisin (20 nM) for 24 h, images of wound-healing assays and Transwell assays were taken at 0 and 24 h. (B) Percent wound closure at 12 and 24 h after scratch is shown (n = 5). (D) The number of cells that migrated to the lower side of the membranes after incubation for 24 h are shown and relative migration was quantified using Image-Pro Plus software (n = 5). Data are mean± SE. ** P< 0.01 vs. irisin-treated group, determined by unpaired two-tailed Student’s t-test.
Mentions: We demonstrated that ERK, not p38 MAPK or AKT signaling pathways were involved in irisin-induced HUVEC proliferation and apoptosis [15]. It was confirmed that phosphorylated ERK (P-ERK) was significantly increased after treatment with irisin for 5 min and 10 min (S1A Fig). To explore whether ERK is involved in HUVEC migration and tube formation, a specific inhibitor of the ERK pathway, U0126, was used to block ERK activation. As shown in Figs 5 and 6, irisin-induced cell migration and tube formation was significantly inhibited by 10 μM U0126. Also, Western blot showed that the irisin-induced increase in ERK phosphorylation was inhibited by pre-treatment with U0126 (S1B and S1C Fig).

Bottom Line: Although our recent evidence supported the contribution of irisin to vascular endothelial cell (ECs) proliferation and apoptosis, further research of irisin involvement in the angiogenesis of ECs was not conclusive.We also found that irisin activated extracellular signal-related kinase (ERK) signaling pathways.Inhibition of ERK signaling by using U0126 decreased the pro-migration and pro-angiogenic effect of irisin on HUVEC.

View Article: PubMed Central - PubMed

Affiliation: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P.R. China.

ABSTRACT
As a link between exercise and metabolism, irisin is assumed to be involved in increased total body energy expenditure, reduced body weight, and increased insulin sensitivity. Although our recent evidence supported the contribution of irisin to vascular endothelial cell (ECs) proliferation and apoptosis, further research of irisin involvement in the angiogenesis of ECs was not conclusive. In the current study, it was found that irisin promoted Human Umbilical Vein Endothelial Cell (HUVEC) angiogenesis via increasing migration and tube formation, and attenuated chemically-induced intersegmental vessel (ISV) angiogenic impairment in transgenic TG (fli1: GFP) zebrafish. It was further demonstrated that expression of matrix metalloproteinase (MMP) 2 and 9 were also up-regulated in endothelial cells. We also found that irisin activated extracellular signal-related kinase (ERK) signaling pathways. Inhibition of ERK signaling by using U0126 decreased the pro-migration and pro-angiogenic effect of irisin on HUVEC. Also, U0126 inhibited the elevated expression of MMP-2 and MMP-9 when they were treated with irisin. In summary, these findings provided direct evidence that irisin may play a pivotal role in maintaining endothelium homeostasis by promoting endothelial cell angiogenesis via the ERK signaling pathway.

No MeSH data available.


Related in: MedlinePlus