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Article: Emodin ameliorates glucose-induced matrix synthesis in human peritoneal mesothelial cells

TitleEmodin ameliorates glucose-induced matrix synthesis in human peritoneal mesothelial cells
Authors
Issue Date2003
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ki/index.html
Citation
Kidney International, 2003, v. 64 n. 2, p. 519-533 How to Cite?
AbstractBackground. Prolonged exposure of human peritoneal mesothelial cells (HPMC) to high glucose concentrations in peritoneal dialysate is the principal factor leading to matrix accumulation and thickening of the peritoneal membrane, accompanied by progressive deterioration of transport functions. These changes are mediated in part through protein kinase C (PKC) activation and the induction of transforming growth factor-beta 1 (TGF-β1). Emodin (3-methyl-1,6,8 trihydroxyanthraquinone) has previously been demonstrated to reduce cell proliferation and fibronectin synthesis in cultured mesangial cells. How emodin modulates glucose-induced abnormalities in HPMC has not been elucidated and thus constitutes the theme of this study. Methods. We investigated the effects of emodin on the expression of PKCα, TGF-β1, fibronectin, and collagen type I in HPMC, and its effects on HPMC proliferation under physiologic (5 mmol) or high (30 mmol) glucose concentrations. Results. Exposure of HPMC cultured with 5 mmol or 30 mmol D-glucose to emodin (20 μg/mL) resulted in an initial lag of proliferation by 2.3 to 2.7 days, but did not affect cell viability or morphology at confluence. D-glucose (30 mmol) induced TGF-β1 secretion in a time-dependent manner (3.72 ± 0.29 and 4.30 ± 0.50 pg/μg cellular protein at 24 hours and 48 hours respectively, compared to 2.13 ± 0.23 and 2.65 ± 0.32 pg/μg cellular protein at 24 hours and 48 hours, respectively for 5 mmol glucose; P < 0.001 at both time points). Such induction was ameliorated by emodin (20 μg/mL) (TGF-β1 concentration 2.25 ± 0.15 and 2.96 ± 0.33 pg/μg cellular protein at 24 hours and 48 hours, respectively, in the presence of emodin and 30 mmol D-glucose; P < 0.001 compared to 30 mmol D-glucose alone at both time points). Induction of TGF-β1 synthesis by 30 mmol D-glucose was associated with induction of PKCα, phosphorylation of cAMP-responsive element binding protein (CREB) and activating transcription factor-1 (ATF-1), and increased fibronectin and type I collagen translation. Emodin abrogated all these effects of concentrated glucose. Immunohistochemical staining showed that 30 mmol D-glucose induced cytoplasmic, perinuclear, and extracellular fibronectin and type I collagen expression by HPMC. Emodin reduced 30 mmol D-glucose-induced cytoplasmic and extracellular matrix synthesis to near basal levels. Conclusion. Our findings demonstrate that emodin ameliorates the undesirable effects of concentrated glucose on HPMC via suppression of PKC activation and CREB phosphorylation, and suggest that emodin may have a therapeutic potential in the prevention or treatment of glucose-induced structural and functional abnormalities in the peritoneal membrane.
Persistent Identifierhttp://hdl.handle.net/10722/77701
ISSN
2015 Impact Factor: 7.683
2015 SCImago Journal Rankings: 3.181
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, TMen_HK
dc.contributor.authorLeung, JKHen_HK
dc.contributor.authorTsang, RCWen_HK
dc.contributor.authorLiu, ZHen_HK
dc.contributor.authorLi, LSen_HK
dc.contributor.authorYung, Sen_HK
dc.date.accessioned2010-09-06T07:34:46Z-
dc.date.available2010-09-06T07:34:46Z-
dc.date.issued2003en_HK
dc.identifier.citationKidney International, 2003, v. 64 n. 2, p. 519-533en_HK
dc.identifier.issn0085-2538en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77701-
dc.description.abstractBackground. Prolonged exposure of human peritoneal mesothelial cells (HPMC) to high glucose concentrations in peritoneal dialysate is the principal factor leading to matrix accumulation and thickening of the peritoneal membrane, accompanied by progressive deterioration of transport functions. These changes are mediated in part through protein kinase C (PKC) activation and the induction of transforming growth factor-beta 1 (TGF-β1). Emodin (3-methyl-1,6,8 trihydroxyanthraquinone) has previously been demonstrated to reduce cell proliferation and fibronectin synthesis in cultured mesangial cells. How emodin modulates glucose-induced abnormalities in HPMC has not been elucidated and thus constitutes the theme of this study. Methods. We investigated the effects of emodin on the expression of PKCα, TGF-β1, fibronectin, and collagen type I in HPMC, and its effects on HPMC proliferation under physiologic (5 mmol) or high (30 mmol) glucose concentrations. Results. Exposure of HPMC cultured with 5 mmol or 30 mmol D-glucose to emodin (20 μg/mL) resulted in an initial lag of proliferation by 2.3 to 2.7 days, but did not affect cell viability or morphology at confluence. D-glucose (30 mmol) induced TGF-β1 secretion in a time-dependent manner (3.72 ± 0.29 and 4.30 ± 0.50 pg/μg cellular protein at 24 hours and 48 hours respectively, compared to 2.13 ± 0.23 and 2.65 ± 0.32 pg/μg cellular protein at 24 hours and 48 hours, respectively for 5 mmol glucose; P < 0.001 at both time points). Such induction was ameliorated by emodin (20 μg/mL) (TGF-β1 concentration 2.25 ± 0.15 and 2.96 ± 0.33 pg/μg cellular protein at 24 hours and 48 hours, respectively, in the presence of emodin and 30 mmol D-glucose; P < 0.001 compared to 30 mmol D-glucose alone at both time points). Induction of TGF-β1 synthesis by 30 mmol D-glucose was associated with induction of PKCα, phosphorylation of cAMP-responsive element binding protein (CREB) and activating transcription factor-1 (ATF-1), and increased fibronectin and type I collagen translation. Emodin abrogated all these effects of concentrated glucose. Immunohistochemical staining showed that 30 mmol D-glucose induced cytoplasmic, perinuclear, and extracellular fibronectin and type I collagen expression by HPMC. Emodin reduced 30 mmol D-glucose-induced cytoplasmic and extracellular matrix synthesis to near basal levels. Conclusion. Our findings demonstrate that emodin ameliorates the undesirable effects of concentrated glucose on HPMC via suppression of PKC activation and CREB phosphorylation, and suggest that emodin may have a therapeutic potential in the prevention or treatment of glucose-induced structural and functional abnormalities in the peritoneal membrane.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ki/index.htmlen_HK
dc.relation.ispartofKidney Internationalen_HK
dc.subject.meshBiopsyen_HK
dc.subject.meshCarcinogens - pharmacologyen_HK
dc.subject.meshCell Division - drug effectsen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshCollagen Type I - metabolismen_HK
dc.subject.meshCyclic AMP Response Element-Binding Protein - metabolismen_HK
dc.subject.meshEmodin - pharmacologyen_HK
dc.subject.meshEnzyme Inhibitors - pharmacologyen_HK
dc.subject.meshEpithelial Cells - drug effects - metabolismen_HK
dc.subject.meshEpitheliumen_HK
dc.subject.meshExtracellular Matrix Proteins - metabolismen_HK
dc.subject.meshFibronectins - metabolismen_HK
dc.subject.meshGlucose - pharmacologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshPeritoneum - cytologyen_HK
dc.subject.meshPhosphorylation - drug effectsen_HK
dc.subject.meshProtein Kinase C - metabolismen_HK
dc.subject.meshProtein Kinase C-alphaen_HK
dc.subject.meshProtein-Tyrosine Kinases - metabolismen_HK
dc.subject.meshTetradecanoylphorbol Acetate - pharmacologyen_HK
dc.subject.meshTransforming Growth Factor beta - metabolismen_HK
dc.subject.meshTransforming Growth Factor beta1en_HK
dc.titleEmodin ameliorates glucose-induced matrix synthesis in human peritoneal mesothelial cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0085-2538&volume=64&issue=2&spage=519&epage=533&date=2003&atitle=Emodin+ameliorates+glucose-induced+matrix+synthesis+in+human+peritoneal+mesothelial+cellsen_HK
dc.identifier.emailChan, TM:dtmchan@hku.hken_HK
dc.identifier.emailYung, S:ssyyung@hku.hken_HK
dc.identifier.authorityChan, TM=rp00394en_HK
dc.identifier.authorityYung, S=rp00455en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1046/j.1523-1755.2003.00113.xen_HK
dc.identifier.pmid12846747en_HK
dc.identifier.scopuseid_2-s2.0-0038119566en_HK
dc.identifier.hkuros81808en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0038119566&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume64en_HK
dc.identifier.issue2en_HK
dc.identifier.spage519en_HK
dc.identifier.epage533en_HK
dc.identifier.isiWOS:000183966500014-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChan, TM=7402687700en_HK
dc.identifier.scopusauthoridLeung, JKH=7202180353en_HK
dc.identifier.scopusauthoridTsang, RCW=36808555100en_HK
dc.identifier.scopusauthoridLiu, ZH=36063537300en_HK
dc.identifier.scopusauthoridLi, LS=7501449836en_HK
dc.identifier.scopusauthoridYung, S=22636568800en_HK
dc.identifier.citeulike2333224-

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