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Article: Diabetic tubulopathy: An emerging entity

TitleDiabetic tubulopathy: An emerging entity
Authors
Issue Date2011
PublisherS Karger AG. The Journal's web site is located at http://www.karger.com/CONEP
Citation
Contributions To Nephrology, 2011, v. 170, p. 124-134 How to Cite?
AbstractIn chronic glomerulopathic disease, renal function correlates more with the degree oftubulointerstitial injury than that of the glomerular lesions. Proteinuria may be one of the pathologic links between these two intrarenal compartments. It is apparent that the proximal tubular epithelial cell (PTEC) assumes a proinflammatory and profibrotic role during proteinuria in which the PTEC expresses a variety of chemokines and injury signals that culminate in progressive interstitial inflammation and fibrosis. During diabetes, other substrates including advanced glycation end products (AGEs), AGE intermediates, and high glucose (HG) may provoke the PTEC even further. Glycated albumin, but not the equivalent dose of bovine serum albumin (BSA), stimulates tubular IL-8 and ICAM-1 expression via NF-κB-, MAPK- and STAT-1-dependent pathways. Human biopsies of diabetic nephropathy (DN) reveal colocalization of AGE and ICAM-1 in proximal tubules. The biologically active carbonyl intermediates methylglyoxal-BSA-AGE and AGE-BSA upregulate tubular expression of CTGF, TGF-β, and VEGF, whereas carboxymethyllysine-BSA stimulates tubular expression of IL-6, CCL-2, CTGF, TGF-β, and VEGF via RAGE activation and NF-κB signal transduction. Hyperglycemia (30 mM), but not the equivalent dose of mannitol, promotes proinflammatory (IL-6 and CCL-2), profibrotic (TGF-β) and angiogenic (VEGF) responses in tubular cells via MAPK and PKC signaling and induces epithelial mesenchymal transition, which is TGF-β1 mediated. It has recently been shown that toll-like receptor (TLR) is implicated in the diabetic kidney. In human DN biopsies and PTEC, TLR4is upregulated and plays a permissive role in HG-induced IL-6 and CCL-2 overexpression and monocyte transmigration. In streptozotocin-induced rat DN and PTEC, TLR2 appears to be upregulated. Other novel mediators that become activated in PTEC exposed to HG include macrophage inflammatory protein-3-α, Krüppel-like factor 6 and thioredoxin-interacting protein, which may be attenuated by peroxisome proliferator-activate dreceptor-γ activation. Collectively, these phenomena suggest that the renal tubules are heavily involved in the pathogenesis of DN. These pathophysiologic responses may be collectively described as diabetic tubulopathy. Copyright © 2011 S. Karger AG, Basel.
Persistent Identifierhttp://hdl.handle.net/10722/137405
ISSN
2015 Impact Factor: 2.438
2015 SCImago Journal Rankings: 0.494
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTang, SCWen_HK
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorLai, KNen_HK
dc.date.accessioned2011-08-26T14:24:27Z-
dc.date.available2011-08-26T14:24:27Z-
dc.date.issued2011en_HK
dc.identifier.citationContributions To Nephrology, 2011, v. 170, p. 124-134en_HK
dc.identifier.issn0302-5144en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137405-
dc.description.abstractIn chronic glomerulopathic disease, renal function correlates more with the degree oftubulointerstitial injury than that of the glomerular lesions. Proteinuria may be one of the pathologic links between these two intrarenal compartments. It is apparent that the proximal tubular epithelial cell (PTEC) assumes a proinflammatory and profibrotic role during proteinuria in which the PTEC expresses a variety of chemokines and injury signals that culminate in progressive interstitial inflammation and fibrosis. During diabetes, other substrates including advanced glycation end products (AGEs), AGE intermediates, and high glucose (HG) may provoke the PTEC even further. Glycated albumin, but not the equivalent dose of bovine serum albumin (BSA), stimulates tubular IL-8 and ICAM-1 expression via NF-κB-, MAPK- and STAT-1-dependent pathways. Human biopsies of diabetic nephropathy (DN) reveal colocalization of AGE and ICAM-1 in proximal tubules. The biologically active carbonyl intermediates methylglyoxal-BSA-AGE and AGE-BSA upregulate tubular expression of CTGF, TGF-β, and VEGF, whereas carboxymethyllysine-BSA stimulates tubular expression of IL-6, CCL-2, CTGF, TGF-β, and VEGF via RAGE activation and NF-κB signal transduction. Hyperglycemia (30 mM), but not the equivalent dose of mannitol, promotes proinflammatory (IL-6 and CCL-2), profibrotic (TGF-β) and angiogenic (VEGF) responses in tubular cells via MAPK and PKC signaling and induces epithelial mesenchymal transition, which is TGF-β1 mediated. It has recently been shown that toll-like receptor (TLR) is implicated in the diabetic kidney. In human DN biopsies and PTEC, TLR4is upregulated and plays a permissive role in HG-induced IL-6 and CCL-2 overexpression and monocyte transmigration. In streptozotocin-induced rat DN and PTEC, TLR2 appears to be upregulated. Other novel mediators that become activated in PTEC exposed to HG include macrophage inflammatory protein-3-α, Krüppel-like factor 6 and thioredoxin-interacting protein, which may be attenuated by peroxisome proliferator-activate dreceptor-γ activation. Collectively, these phenomena suggest that the renal tubules are heavily involved in the pathogenesis of DN. These pathophysiologic responses may be collectively described as diabetic tubulopathy. Copyright © 2011 S. Karger AG, Basel.en_HK
dc.languageengen_US
dc.publisherS Karger AG. The Journal's web site is located at http://www.karger.com/CONEPen_HK
dc.relation.ispartofContributions to Nephrologyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshDiabetic Nephropathies - etiologyen_HK
dc.subject.meshEpithelial Cells - physiologyen_HK
dc.subject.meshGlycosylation End Products, Advanced - physiologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIntercellular Adhesion Molecule-1 - physiologyen_HK
dc.subject.meshKidney Tubules, Proximal - physiologyen_HK
dc.subject.meshMAP Kinase Signaling Systemen_HK
dc.subject.meshToll-Like Receptors - physiologyen_HK
dc.titleDiabetic tubulopathy: An emerging entityen_HK
dc.typeArticleen_HK
dc.identifier.emailTang, SCW: scwtang@hku.hken_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailLai, KN: knlai@hku.hken_HK
dc.identifier.authorityTang, SCW=rp00480en_HK
dc.identifier.authorityLeung, JCK=rp00448en_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1159/000325647en_HK
dc.identifier.pmid21659765-
dc.identifier.scopuseid_2-s2.0-79959216929en_HK
dc.identifier.hkuros190796en_US
dc.identifier.hkuros190951-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79959216929&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume170en_HK
dc.identifier.spage124en_HK
dc.identifier.epage134en_HK
dc.identifier.isiWOS:000292615800014-
dc.publisher.placeSwitzerlanden_HK
dc.identifier.scopusauthoridTang, SCW=7403437082en_HK
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK

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