Abstract
Diabetic status is characterized by chronic low-grade inflammation and an increased burden of senescent cells. Recently, the senescence-associated secretory phenotype (SASP) has been suggested as a possible source of inflammatory factors in obesity-induced type 2 diabetes. However, while senescence is a known consequence of hyperglycaemia, evidences of SASP as a result of the glycaemic insult are missing. In addition, few data are available regarding which cell types are the main SASP-spreading cells in vivo. Adopting a four-pronged approach we demonstrated that: i) an archetypal SASP response that was at least partly attributable to endothelial cells and macrophages is induced in mouse kidney after in vivo exposure to sustained hyperglycaemia; ii) reproducing a similar condition in vitro in endothelial cells and macrophages, hyperglycaemic stimulus largely phenocopies the SASP acquired during replicative senescence; iii) in endothelial cells, hyperglycaemia-induced senescence and SASP could be prevented by SOD-1 overexpression; and iiii) ex vivo circulating angiogenic cells derived from peripheral blood mononuclear cells from diabetic patients displayed features consistent with the SASP. Overall, the present findings document a direct link between hyperglycaemia and the SASP in endothelial cells and macrophages, making the SASP a highly likely contributor to the fuelling of low-grade inflammation in diabetes.
| Original language | English |
|---|---|
| Pages (from-to) | 1-12 |
| Number of pages | 12 |
| Journal | Redox Biology |
| DOIs | |
| Publication status | E-pub ahead of print - Dec 6 2017 |
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Short-term sustained hyperglycaemia fosters an archetypal senescence-associated secretory phenotype in endothelial cells and macrophages. / Prattichizzo, Francesco; De Nigris, Valeria; Mancuso, Elettra; Spiga, Rosangela; Giuliani, Angelica; Matacchione, Giulia; Lazzarini, Raffaella; Marcheselli, Fiorella; Recchioni, Rina; Testa, Roberto; La Sala, Lucia; Rippo, Maria Rita; Procopio, Antonio Domenico; Olivieri, Fabiola; Ceriello, Antonio.
In: Redox Biology, 06.12.2017, p. 1-12.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Short-term sustained hyperglycaemia fosters an archetypal senescence-associated secretory phenotype in endothelial cells and macrophages
AU - Prattichizzo, Francesco
AU - De Nigris, Valeria
AU - Mancuso, Elettra
AU - Spiga, Rosangela
AU - Giuliani, Angelica
AU - Matacchione, Giulia
AU - Lazzarini, Raffaella
AU - Marcheselli, Fiorella
AU - Recchioni, Rina
AU - Testa, Roberto
AU - La Sala, Lucia
AU - Rippo, Maria Rita
AU - Procopio, Antonio Domenico
AU - Olivieri, Fabiola
AU - Ceriello, Antonio
N1 - Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2017/12/6
Y1 - 2017/12/6
N2 - Diabetic status is characterized by chronic low-grade inflammation and an increased burden of senescent cells. Recently, the senescence-associated secretory phenotype (SASP) has been suggested as a possible source of inflammatory factors in obesity-induced type 2 diabetes. However, while senescence is a known consequence of hyperglycaemia, evidences of SASP as a result of the glycaemic insult are missing. In addition, few data are available regarding which cell types are the main SASP-spreading cells in vivo. Adopting a four-pronged approach we demonstrated that: i) an archetypal SASP response that was at least partly attributable to endothelial cells and macrophages is induced in mouse kidney after in vivo exposure to sustained hyperglycaemia; ii) reproducing a similar condition in vitro in endothelial cells and macrophages, hyperglycaemic stimulus largely phenocopies the SASP acquired during replicative senescence; iii) in endothelial cells, hyperglycaemia-induced senescence and SASP could be prevented by SOD-1 overexpression; and iiii) ex vivo circulating angiogenic cells derived from peripheral blood mononuclear cells from diabetic patients displayed features consistent with the SASP. Overall, the present findings document a direct link between hyperglycaemia and the SASP in endothelial cells and macrophages, making the SASP a highly likely contributor to the fuelling of low-grade inflammation in diabetes.
AB - Diabetic status is characterized by chronic low-grade inflammation and an increased burden of senescent cells. Recently, the senescence-associated secretory phenotype (SASP) has been suggested as a possible source of inflammatory factors in obesity-induced type 2 diabetes. However, while senescence is a known consequence of hyperglycaemia, evidences of SASP as a result of the glycaemic insult are missing. In addition, few data are available regarding which cell types are the main SASP-spreading cells in vivo. Adopting a four-pronged approach we demonstrated that: i) an archetypal SASP response that was at least partly attributable to endothelial cells and macrophages is induced in mouse kidney after in vivo exposure to sustained hyperglycaemia; ii) reproducing a similar condition in vitro in endothelial cells and macrophages, hyperglycaemic stimulus largely phenocopies the SASP acquired during replicative senescence; iii) in endothelial cells, hyperglycaemia-induced senescence and SASP could be prevented by SOD-1 overexpression; and iiii) ex vivo circulating angiogenic cells derived from peripheral blood mononuclear cells from diabetic patients displayed features consistent with the SASP. Overall, the present findings document a direct link between hyperglycaemia and the SASP in endothelial cells and macrophages, making the SASP a highly likely contributor to the fuelling of low-grade inflammation in diabetes.
U2 - 10.1016/j.redox.2017.12.001
DO - 10.1016/j.redox.2017.12.001
M3 - Article
C2 - 29253812
SP - 1
EP - 12
JO - Redox Biology
JF - Redox Biology
SN - 2213-2317
ER -