SIRT1 Inhibition Affects Angiogenic Properties of Human MSCs
Joint Authors
Chiara, Botti
Ilaria, Caiafa
Antonietta, Coppola
Francesca, Cuomo
Marco, Miceli
Lucia, Altucci
Gilda, Cobellis
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-08-26
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Human mesenchymal stem cells (hMSCs) are attractive for clinical and experimental purposes due to their capability of self-renewal and of differentiating into several cell types.
Autologous hMSCs transplantation has been proven to induce therapeutic angiogenesis in ischemic disorders.
However, the molecular mechanisms underlying these effects remain unclear.
A recent report has connected MSCs multipotency to sirtuin families, showing that SIRT1 can regulate MSCs function.
Furthermore, SIRT1 is a critical modulator of endothelial angiogenic functions.
Here, we described the generation of an immortalized human mesenchymal bone marrow-derived cell line and we investigated the angiogenic phenotype of our cellular model by inhibiting SIRT1 by both the genetic and pharmacological level.
We first assessed the expression of SIRT1 in hMSCs under basal and hypoxic conditions at both RNA and protein level.
Inhibition of SIRT1 by sirtinol, a cell-permeable inhibitor, or by specific sh-RNA resulted in an increase of premature-senescence phenotype, a reduction of proliferation rate with increased apoptosis.
Furthermore, we observed a consistent reduction of tubule-like formation and migration and we found that SIRT1 inhibition reduced the hypoxia induced accumulation of HIF-1α protein and its transcriptional activity in hMSCs.
Our findings identify SIRT1 as regulator of hypoxia-induced response in hMSCs and may contribute to the development of new therapeutic strategies to improve regenerative properties of mesenchymal stem cells in ischemic disorders through SIRT1 modulation.
American Psychological Association (APA)
Chiara, Botti& Ilaria, Caiafa& Antonietta, Coppola& Francesca, Cuomo& Marco, Miceli& Lucia, Altucci…[et al.]. 2014. SIRT1 Inhibition Affects Angiogenic Properties of Human MSCs. BioMed Research International،Vol. 2014, no. 2014, pp.1-12.
https://search.emarefa.net/detail/BIM-1016556
Modern Language Association (MLA)
Chiara, Botti…[et al.]. SIRT1 Inhibition Affects Angiogenic Properties of Human MSCs. BioMed Research International No. 2014 (2014), pp.1-12.
https://search.emarefa.net/detail/BIM-1016556
American Medical Association (AMA)
Chiara, Botti& Ilaria, Caiafa& Antonietta, Coppola& Francesca, Cuomo& Marco, Miceli& Lucia, Altucci…[et al.]. SIRT1 Inhibition Affects Angiogenic Properties of Human MSCs. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-12.
https://search.emarefa.net/detail/BIM-1016556
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1016556