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.

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. - ISSN 2213-2317. - ELETTRONICO. - 15:(2018), pp. 170-181. [10.1016/j.redox.2017.12.001]

Short-term sustained hyperglycaemia fosters an archetypal senescence-associated secretory phenotype in endothelial cells and macrophages

Prattichizzo, Francesco
;
Giuliani, Angelica;Matacchione, Giulia;Lazzarini, Raffaella;La Sala, Lucia;Rippo, Maria Rita;Procopio, Antonio Domenico;Olivieri, Fabiola;
2018-01-01

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.
2018
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/252937
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