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2014 ; 52
(2
): 77-85
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Upregulation of IGF2 expression during vascular calcification
#MMPMID24482492
Zhu D
; Mackenzie NC
; Millan JL
; Farquharson C
; Macrae VE
J Mol Endocrinol
2014[Apr]; 52
(2
): 77-85
PMID24482492
show ga
The process of vascular calcification shares many similarities with that of
skeletal mineralisation and involves the deposition of hydroxyapatite crystals in
arteries and cardiac valves. However, the cellular mechanisms responsible have
yet to be fully elucidated. In this study, we employed microarray analysis to
demonstrate the upregulation of more than >9000 genes during the calcification of
murine vascular smooth muscle cells (VSMCs), of which the most significantly,
differentially expressed gene was Igf2. Following the validation of increased
IGF2 expression by RT-qPCR and immunoblotting in calcifying murine VSMCs, IGF2
expression was further demonstrated in the calcified aorta of the Enpp1(-/-)
mouse model of medial aortic calcification. Having confirmed that IGF1R and IGF2R
were expressed in cultured murine VSMCs, cell-signalling studies in these cells
revealed that IGF2 (50 ng/ml) significantly stimulated the phosphorylation of Akt
and Erk1/2 (P<0.05). These results potentially indicate that IGF2 may mediate
VSMC calcification via the stimulation of Erk1/2 and Akt signalling. This study
suggests that the increased IGF2 expression in calcifying VSMCs may reflect the
well-established prenatal role of IGF2, particularly as the osteogenic phenotypic
transition of VSMCs in a calcified environment recapitulates many of the events
occurring during embryonic development. A full understanding of the importance of
IGF2 in this pathological process will lead to a better understanding of the
aetiology of vascular calcification.
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