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Article: Serum Level of Soluble Receptor for Advanced Glycation End Products Is Associated with A Disintegrin And Metalloproteinase 10 in Type 1 Diabetes

TitleSerum Level of Soluble Receptor for Advanced Glycation End Products Is Associated with A Disintegrin And Metalloproteinase 10 in Type 1 Diabetes
Authors
Issue Date2015
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2015, v. 10 n. 9, p. e0137330 How to Cite?
AbstractBackground The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic complications, and soluble forms of the receptor (sRAGE) can counteract the detrimental action of the full-length receptor by acting as decoy. Soluble RAGE is produced by alternative splicing [endogenous secretory RAGE (esRAGE)] and/or by proteolytic cleavage of the membrane-bound receptor. We have investigated the role of A Disintegrin And Metalloproteinase 10 (ADAM10) in the ectodomain shedding of RAGE. Methods Constitutive and insulin-induced shedding of RAGE in THP-1 macrophages by ADAM10 was evaluated using an ADAM10-specific metalloproteinase inhibitor. Serum ADAM10 level was measured in type 1 diabetes and control subjects, and the association with serum soluble RAGE was determined. Serum total sRAGE and esRAGE were assayed by ELISA and the difference between total sRAGE and esRAGE gave an estimated measure of soluble RAGE formed by cleavage (cRAGE). Results RAGE shedding (constitutive and insulin-induced) was significantly reduced after inhibition of ADAM10 in macrophages, and insulin stimulated ADAM10 expression and activity. Diabetic subjects have higher serum total sRAGE and esRAGE (p<0.01) than controls, and serum ADAM10 was also increased (p<0.01). Serum ADAM10 correlated with serum cRAGE in type 1 diabetes (r = 0.40, p<0.01) and in controls (r = 0.31. p<0.01) but no correlations were seen with esRAGE. The association remained significant after adjusting for age, gender, BMI, smoking status and HbA1c. Conclusion Our data suggested that ADAM10 contributed to the shedding of RAGE. Serum ADAM10 level was increased in type 1 diabetes and was a significant determinant of circulating cRAGE.
Persistent Identifierhttp://hdl.handle.net/10722/227824
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
ISI Accession Number ID
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DC FieldValueLanguage
dc.contributor.authorLee, ACH-
dc.contributor.authorLam, JKY-
dc.contributor.authorShiu, SWM-
dc.contributor.authorWong, Y-
dc.contributor.authorBetteridge, DJ-
dc.contributor.authorTan, KCB-
dc.date.accessioned2016-07-19T07:19:11Z-
dc.date.available2016-07-19T07:19:11Z-
dc.date.issued2015-
dc.identifier.citationPlos One, 2015, v. 10 n. 9, p. e0137330-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/227824-
dc.description.abstractBackground The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic complications, and soluble forms of the receptor (sRAGE) can counteract the detrimental action of the full-length receptor by acting as decoy. Soluble RAGE is produced by alternative splicing [endogenous secretory RAGE (esRAGE)] and/or by proteolytic cleavage of the membrane-bound receptor. We have investigated the role of A Disintegrin And Metalloproteinase 10 (ADAM10) in the ectodomain shedding of RAGE. Methods Constitutive and insulin-induced shedding of RAGE in THP-1 macrophages by ADAM10 was evaluated using an ADAM10-specific metalloproteinase inhibitor. Serum ADAM10 level was measured in type 1 diabetes and control subjects, and the association with serum soluble RAGE was determined. Serum total sRAGE and esRAGE were assayed by ELISA and the difference between total sRAGE and esRAGE gave an estimated measure of soluble RAGE formed by cleavage (cRAGE). Results RAGE shedding (constitutive and insulin-induced) was significantly reduced after inhibition of ADAM10 in macrophages, and insulin stimulated ADAM10 expression and activity. Diabetic subjects have higher serum total sRAGE and esRAGE (p<0.01) than controls, and serum ADAM10 was also increased (p<0.01). Serum ADAM10 correlated with serum cRAGE in type 1 diabetes (r = 0.40, p<0.01) and in controls (r = 0.31. p<0.01) but no correlations were seen with esRAGE. The association remained significant after adjusting for age, gender, BMI, smoking status and HbA1c. Conclusion Our data suggested that ADAM10 contributed to the shedding of RAGE. Serum ADAM10 level was increased in type 1 diabetes and was a significant determinant of circulating cRAGE.-
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPlos One-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleSerum Level of Soluble Receptor for Advanced Glycation End Products Is Associated with A Disintegrin And Metalloproteinase 10 in Type 1 Diabetes-
dc.typeArticle-
dc.identifier.emailWong, Y: ywong@hkucc.hku.hk-
dc.identifier.emailTan, KCB: kcbtan@hku.hk-
dc.identifier.authorityTan, KCB=rp00402-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0137330-
dc.identifier.pmid26325204-
dc.identifier.hkuros262402-
dc.identifier.volume10-
dc.identifier.issue9-
dc.identifier.spagee0137330-
dc.identifier.epagee0137330-
dc.identifier.isiWOS:000360437700111-
dc.publisher.placeUnited States-
dc.relation.projectAdvanced glycation end product receptors in diabetes-

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