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Article: Enhanced expression of receptor for advanced glycation end-products is associated with low circulating soluble isoforms of the receptor in Type 2 diabetes

TitleEnhanced expression of receptor for advanced glycation end-products is associated with low circulating soluble isoforms of the receptor in Type 2 diabetes
Authors
KeywordsAdvanced glycation end-product (AGE)
Biomarker
Soluble receptor for advanced glycation end-product (sRAGE)
Type 2 diabetes mellitus
Issue Date2011
PublisherPortland Press Ltd. The Journal's web site is located at http://www.clinsci.org/
Citation
Clinical Science, 2011, v. 120 n. 2, p. 81-89 How to Cite?
AbstractThe sRAGE [soluble RAGE (receptor for advanced glycation end-products)] lack the transmembrane and cytoplasmic domain of the full-length receptor and can function as a decoy for RAGE ligands. Recent evidence suggests that sRAGE may be a potential biomarker of RAGE-mediated pathology. The present study aimed to examine the relationship between RAGE expression in peripheral blood monocytes and circulating sRAGE and esRAGE (endogenous sRAGE, a splice variant of sRAGE) in Type 2 diabetes. Protein expression of RAGE and esRAGE in monocyte cell lysate was determined by Western blot in 53 diabetic patients and 52 controls. Monocyte cell-surface-bound full-length RAGE expression was measured using flow cytometry. Serum sRAGE, esRAGE and AGE (advanced glycation end products) were assayed by ELISA. The mean HbA 1c (glycated haemoglobin) of the diabetic patients was 9.74% and serum AGEs was increased. Monocyte full-length RAGE expression was significantly higher in diabetic patients whereas esRAGE expression was reduced, and serum AGEs concentration was an independent determinant of monocyte cell surface full-length RAGE expression. Serum levels of sRAGE [573.3 (375.7-754.3) compared with 608.1 (405.3-940.8) pg/ml, P < 0.05] and esRAGE [241.8 (154.6-356.6) compared with 286.5 (202.6-390.0) pg/ml, P < 0.05; values are medians (interquartile range)] were decreased. There was an inverse association between monocyte RAGE expression and log(serum sRAGE) (r = - 0.34, P = 0.01) but not with esRAGE. In conclusion, despite an increase in full-length RAGE expression, esRAGE expression was down-regulated in the diabetic patients, and serum sRAGE and esRAGE was also reduced. Hence increased full-length RAGE levels are not associated with a similar increase in sRAGE isoforms levels. © The Authors Journal compilation © 2011 Biochemical Society.
Persistent Identifierhttp://hdl.handle.net/10722/135246
ISSN
2023 Impact Factor: 6.7
2023 SCImago Journal Rankings: 1.565
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 775708M
Funding Information:

This study was supported by the Hong Kong Research Grants Council Research Fund [grant number HKU 775708M].

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorTam, XHLen_HK
dc.contributor.authorShiu, SWMen_HK
dc.contributor.authorLeng, Len_HK
dc.contributor.authorBucala, Ren_HK
dc.contributor.authorBetteridge, DJen_HK
dc.contributor.authorTan, KCBen_HK
dc.date.accessioned2011-07-27T01:30:31Z-
dc.date.available2011-07-27T01:30:31Z-
dc.date.issued2011en_HK
dc.identifier.citationClinical Science, 2011, v. 120 n. 2, p. 81-89en_HK
dc.identifier.issn0143-5221en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135246-
dc.description.abstractThe sRAGE [soluble RAGE (receptor for advanced glycation end-products)] lack the transmembrane and cytoplasmic domain of the full-length receptor and can function as a decoy for RAGE ligands. Recent evidence suggests that sRAGE may be a potential biomarker of RAGE-mediated pathology. The present study aimed to examine the relationship between RAGE expression in peripheral blood monocytes and circulating sRAGE and esRAGE (endogenous sRAGE, a splice variant of sRAGE) in Type 2 diabetes. Protein expression of RAGE and esRAGE in monocyte cell lysate was determined by Western blot in 53 diabetic patients and 52 controls. Monocyte cell-surface-bound full-length RAGE expression was measured using flow cytometry. Serum sRAGE, esRAGE and AGE (advanced glycation end products) were assayed by ELISA. The mean HbA 1c (glycated haemoglobin) of the diabetic patients was 9.74% and serum AGEs was increased. Monocyte full-length RAGE expression was significantly higher in diabetic patients whereas esRAGE expression was reduced, and serum AGEs concentration was an independent determinant of monocyte cell surface full-length RAGE expression. Serum levels of sRAGE [573.3 (375.7-754.3) compared with 608.1 (405.3-940.8) pg/ml, P < 0.05] and esRAGE [241.8 (154.6-356.6) compared with 286.5 (202.6-390.0) pg/ml, P < 0.05; values are medians (interquartile range)] were decreased. There was an inverse association between monocyte RAGE expression and log(serum sRAGE) (r = - 0.34, P = 0.01) but not with esRAGE. In conclusion, despite an increase in full-length RAGE expression, esRAGE expression was down-regulated in the diabetic patients, and serum sRAGE and esRAGE was also reduced. Hence increased full-length RAGE levels are not associated with a similar increase in sRAGE isoforms levels. © The Authors Journal compilation © 2011 Biochemical Society.en_HK
dc.languageengen_US
dc.publisherPortland Press Ltd. The Journal's web site is located at http://www.clinsci.org/en_HK
dc.relation.ispartofClinical Scienceen_HK
dc.rightsThe final version of record is available at [http://www.clinsci.org/cs/default.htm].-
dc.subjectAdvanced glycation end-product (AGE)en_HK
dc.subjectBiomarkeren_HK
dc.subjectSoluble receptor for advanced glycation end-product (sRAGE)en_HK
dc.subjectType 2 diabetes mellitusen_HK
dc.subject.meshBlotting, Western - methods-
dc.subject.meshDiabetes Mellitus, Type 2 - blood-
dc.subject.meshGlycosylation End Products, Advanced - blood-
dc.subject.meshHemoglobin A, Glycosylated - metabolism-
dc.subject.meshReceptors, Immunologic - blood - genetics-
dc.titleEnhanced expression of receptor for advanced glycation end-products is associated with low circulating soluble isoforms of the receptor in Type 2 diabetesen_HK
dc.typeArticleen_HK
dc.identifier.emailTan, KCB:kcbtan@hku.hken_HK
dc.identifier.authorityTan, KCB=rp00402en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1042/CS20100256en_HK
dc.identifier.pmid20726839-
dc.identifier.scopuseid_2-s2.0-78650853295en_HK
dc.identifier.hkuros188209en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78650853295&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume120en_HK
dc.identifier.issue2en_HK
dc.identifier.spage81en_HK
dc.identifier.epage89en_HK
dc.identifier.eissn1470-8736-
dc.identifier.isiWOS:000290287000008-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectSoluble receptor for advanced glycation end products and diabetic complications-
dc.identifier.scopusauthoridTam, XHL=37027376000en_HK
dc.identifier.scopusauthoridShiu, SWM=7005550652en_HK
dc.identifier.scopusauthoridLeng, L=7006089148en_HK
dc.identifier.scopusauthoridBucala, R=7102379822en_HK
dc.identifier.scopusauthoridBetteridge, DJ=34973752700en_HK
dc.identifier.scopusauthoridTan, KCB=8082703100en_HK
dc.identifier.issnl0143-5221-

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