AMP-activated protein kinase inhibits insulin-like growth factor-1 signaling in vascular smooth muscle cells via regulating activation of extracellular signal-regulated kinases 1/2

doi:10.3969/j.issn.1006-7795.2019.01.018

Journal of Capital Medical University ›› 2019, Vol. 40 ›› Issue (1): 101-105.doi: 10.3969/j.issn.1006-7795.2019.01.018

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AMP-activated protein kinase inhibits insulin-like growth factor-1 signaling in vascular smooth muscle cells via regulating activation of extracellular signal-regulated kinases 1/2

Ning Junyu^1,2,3, Jing Haiming^1,2, Du Hongju^1,2, Qi Lijuan^1,2, Gao Shan^1,2, Li Guojun^1,2,3

1. Institute of Toxicology, Beijing Center for Disease Control and Prevention, Beijing 100013, China;
2. Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing 100013, China;
3. School of Public Health, Capital Medical University, Beijing 100069, China

Received:2017-07-20 Online:2019-01-21 Published:2019-01-23
Supported by:
This study was supported by National Natural Science Foundation of China (81170268).

Abstract

Abstract: Objective To further demonstrate AMP-activated protein kinase (AMPK) inhibiting IGF-1-stimulated cell proliferation and determine its potential mechanism in porcine aorta vascular smooth muscle cells (pVSMCs). Methods Metformine was utilized to enhance activation of AMPK (shown as increasing phosphorylation level of AMPK at threonine 172). Site-directed mutagenesis was utilized to construct constitutively active AMPK. Short hairpins RNA (shRNA) for AMPK were designed to construct AMPK silencing vectors. AMPK activator metformine, Lenti-virus-mediated expression of constitutively active forms of AMPK and Lenti-virus-mediated AMPK knocking-down were utilized to observe influence of AMPK activity on IGF-1-stimulated activation of extracellular signal-regulated kinases 1/2 (ERK1/2,phospnorylation of ERK1/2 at threonine 202 and tyrosine 204) as well as subsequential cell proliferation in porcine aorta vascular smooth muscle cells. Results The AMPK activator metformine significantly increased phosphorylation of AMPK at thr172 and inhibited IGF-1-stimulated phosphorylation of ERK1/2 at threonine 202 and tyrosine 204(T202/Y204). Constitutively active forms of AMPK were expressed in pVSMCs and suppressed IGF-1-stimulated phosphorylation of ERK1/2 at T202/Y204 and cell proliferation. AMPK expression was significantly decreased in pVSMCs infected with AMPK silencing Lenti-virus. AMPK knocking-down induced higher phosphorylation of ERK1/2 at T202/Y204 upon IGF-1 stimulation in porcine aorta vascular smooth muscle cells. Conclusion AMPK induces inhibition of IGF-1 signaling through suppressing activation of ERK1/2 in porcine aorta vascular smooth muscle cells.

Key words: AMP-activated protein kinase, insulin-like growth factor-1, extracellular signal-regulated kinases 1/2

CLC Number:

Q813

Ning Junyu, Jing Haiming, Du Hongju, Qi Lijuan, Gao Shan, Li Guojun. AMP-activated protein kinase inhibits insulin-like growth factor-1 signaling in vascular smooth muscle cells via regulating activation of extracellular signal-regulated kinases 1/2[J]. Journal of Capital Medical University, 2019, 40(1): 101-105.

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AMP-activated protein kinase inhibits insulin-like growth factor-1 signaling in vascular smooth muscle cells via regulating activation of extracellular signal-regulated kinases 1/2

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