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Article: Distinct role of matrix metalloproteinase-3 in kidney injury molecule-1 shedding by kidney proximal tubular epithelial cells

TitleDistinct role of matrix metalloproteinase-3 in kidney injury molecule-1 shedding by kidney proximal tubular epithelial cells
Authors
KeywordsEctodomain Shedding
Kidney Injury Molecule
Matrix Metalloproteinase
Proximal Tubular Epithelial Cells
Reactive Oxygen Species
Issue Date2012
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/biocel
Citation
International Journal Of Biochemistry And Cell Biology, 2012, v. 44 n. 6, p. 1040-1450 How to Cite?
AbstractTubulointerstitial injury is a common pathway in progressive renal impairment and human proximal tubular epithelial cells (PTEC) play a crucial role in this process. Kidney injury molecule-1 (KIM-1) has received increasing attention due to its potential utility as the therapeutic target and biomarker for kidney injury. This study aims to explore the underlying mechanism regulating the release of KIM-1. Cultured primary human PTEC expressed and released KIM-1 from the apical surface through an ectodomain shedding process mediated by matrix metalloproteinase (MMP), independent of gene expression and protein synthesis. The constitutive KIM-1 shedding by PTEC was enhanced in a dose- and time-dependent manner by human serum albumin (HSA) or tumor necrosis factor-α (TNF-α), two important physiological stimuli found during kidney injury. Data from PCR array screening of MMPs gene expression in PTEC following activation by HSA or TNF-α, and from blocking experiments using either synthetic MMP inhibitors or MMP gene knockdown by siRNA, revealed that the constitutive and accelerated shedding of KIM-1 in cultured PTEC was mediated by MMP-3. Furthermore, the up-regulation of MMP-3 and KIM-1 release by PTEC was associated with generation of reactive oxygen species. In a mouse model of acute kidney injury induced by ischemia and reperfusion, increased expression of MMP-3 and KIM-1 as well as their co-localization were observed in kidney from ischemic but not in sham-operated mice. Taken together, these in vitro and in vivo evidences suggest that MMP-3 plays an inductive role in KIM-1 shedding by PTEC. © 2012 Elsevier Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/163483
ISSN
2015 Impact Factor: 3.905
2015 SCImago Journal Rankings: 2.003
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLim, AIen_US
dc.contributor.authorChan, LYYen_US
dc.contributor.authorLai, KNen_US
dc.contributor.authorTang, SCWen_US
dc.contributor.authorChow, CWen_US
dc.contributor.authorLam, MFen_US
dc.contributor.authorLeung, JCKen_US
dc.date.accessioned2012-09-05T05:31:52Z-
dc.date.available2012-09-05T05:31:52Z-
dc.date.issued2012en_US
dc.identifier.citationInternational Journal Of Biochemistry And Cell Biology, 2012, v. 44 n. 6, p. 1040-1450en_US
dc.identifier.issn1357-2725en_US
dc.identifier.urihttp://hdl.handle.net/10722/163483-
dc.description.abstractTubulointerstitial injury is a common pathway in progressive renal impairment and human proximal tubular epithelial cells (PTEC) play a crucial role in this process. Kidney injury molecule-1 (KIM-1) has received increasing attention due to its potential utility as the therapeutic target and biomarker for kidney injury. This study aims to explore the underlying mechanism regulating the release of KIM-1. Cultured primary human PTEC expressed and released KIM-1 from the apical surface through an ectodomain shedding process mediated by matrix metalloproteinase (MMP), independent of gene expression and protein synthesis. The constitutive KIM-1 shedding by PTEC was enhanced in a dose- and time-dependent manner by human serum albumin (HSA) or tumor necrosis factor-α (TNF-α), two important physiological stimuli found during kidney injury. Data from PCR array screening of MMPs gene expression in PTEC following activation by HSA or TNF-α, and from blocking experiments using either synthetic MMP inhibitors or MMP gene knockdown by siRNA, revealed that the constitutive and accelerated shedding of KIM-1 in cultured PTEC was mediated by MMP-3. Furthermore, the up-regulation of MMP-3 and KIM-1 release by PTEC was associated with generation of reactive oxygen species. In a mouse model of acute kidney injury induced by ischemia and reperfusion, increased expression of MMP-3 and KIM-1 as well as their co-localization were observed in kidney from ischemic but not in sham-operated mice. Taken together, these in vitro and in vivo evidences suggest that MMP-3 plays an inductive role in KIM-1 shedding by PTEC. © 2012 Elsevier Ltd.en_US
dc.languageengen_US
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/biocelen_US
dc.relation.ispartofInternational Journal of Biochemistry and Cell Biologyen_US
dc.subjectEctodomain Sheddingen_US
dc.subjectKidney Injury Moleculeen_US
dc.subjectMatrix Metalloproteinaseen_US
dc.subjectProximal Tubular Epithelial Cellsen_US
dc.subjectReactive Oxygen Speciesen_US
dc.titleDistinct role of matrix metalloproteinase-3 in kidney injury molecule-1 shedding by kidney proximal tubular epithelial cellsen_US
dc.typeArticleen_US
dc.identifier.emailLai, KN:knlai@hku.hken_US
dc.identifier.emailLeung, JCK:jckleung@hku.hken_US
dc.identifier.emailChan, LYY: yychanb@hkucc.hku.hk-
dc.identifier.emailTang, SCW: scwtang@hku.hk-
dc.identifier.emailLam, MF: feimflam@hku.hk-
dc.identifier.authorityLai, KN=rp00324en_US
dc.identifier.authorityLeung, JCK=rp00448en_US
dc.identifier.authorityTang, SCW=rp00480-
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.biocel.2012.03.015en_US
dc.identifier.pmid22484054-
dc.identifier.scopuseid_2-s2.0-84860280763en_US
dc.identifier.hkuros203967-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84860280763&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume44en_US
dc.identifier.issue6en_US
dc.identifier.spage1040en_US
dc.identifier.epage1450en_US
dc.identifier.isiWOS:000304490700026-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLim, AI=52364409600en_US
dc.identifier.scopusauthoridChan, LYY=35336076700en_US
dc.identifier.scopusauthoridLai, KN=7402135706en_US
dc.identifier.scopusauthoridTang, SCW=36103837600en_US
dc.identifier.scopusauthoridChow, CW=52363242400en_US
dc.identifier.scopusauthoridLam, MF=54917612500en_US
dc.identifier.scopusauthoridLeung, JCK=7202180349en_US
dc.identifier.citeulike10527296-

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