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Conference Paper: Anti-inflammatory effects of BMP7 on AGEs-induced tubular injury

TitleAnti-inflammatory effects of BMP7 on AGEs-induced tubular injury
Authors
Issue Date2012
PublisherAmerican Society of Nephrology. The Journal's web site is located at https://www.asn-online.org/abstracts/
Citation
Kidney Week 2012, San Diego, CA., 30 October-4 November 2012. In Journal of the American Society of Nephrology, 2012, v. 23, p. 955A, abstract no. PUB267 How to Cite?
AbstractBACKGROUND: Formation and accumulation of advanced glycation end products (AGEs) are remarkably accelerated in the diabetic kidney. We recently demonstrated that AGEs stimulated various pro-inflammatory and pro-fibrotic responses in cultured human proximal tubular epithelial cells (PTEC). Bone morphogenetic protein (BMP) 7 has been reported to confer renoprotective effects in a variety of cell types and disease models. However, data is lacking in AGEs-induced renal tubular inflammation. Our present study explored the therapeutic potential of BMP7 on AGEs-induced tubular injury and its possible mechanisms. METHODS: Primary human PTEC were growth-arrested and exposed to glycated human serum albumin (AGE-HSA) with or without recombinant human BMP7 (rhBMP7). Pro-inflammatory chemokines and cytokines were detected at both gene and protein levels by real-time PCR and ELISA, respectively. Inhibitors of different signaling pathways were used (SB203580, PD98059 and PDTC for p38 MAPK, p44/42 MAPK and NF-κB respectively) to study the involvement of these pathways. RESULTS: AGE-HSA induced PTEC expression of pro-inflammatory factors through multiple pathways - IL8 through both p38 and p44/42 MAPK pathways, sICAM-1 through p44/42, and MCP1 through p38 MAPK. Although PDTC suppressed the mRNA and protein expression of IL-6 and TNF-α induced by AGE-HSA, AGE failed to stimulate NF-κB under these experimental conditions, indicating involvement of other pathways. rhBMP7 (5-200 ng/mL) dose-dependently attenuated AGE-HSA (100 ug/mL)-induced expression of sICAM-1, MCP1, IL8, TNF-α and IL6 at both mRNA and protein levels. Moreover, rhBMP7 suppressed phosphorylation of p38, p44/42 which was induced by AGE-HSA. CONCLUSIONS: Our in vitro results demonstrated that BMP7 can attenuate pro-inflammatory responses to AGE stimulation in PTEC via suppression of multiple signaling pathways including p38 and p44/42 MAPK. Its potential application as a therapeutic molecule warrants further investigation.
DescriptionPublication Only: no. PUB267
Persistent Identifierhttp://hdl.handle.net/10722/186849
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699

 

DC FieldValueLanguage
dc.contributor.authorLi, Ren_US
dc.contributor.authorYiu, WHen_US
dc.contributor.authorLin, Men_US
dc.contributor.authorWu, Hen_US
dc.contributor.authorChan, LYYen_US
dc.contributor.authorLeung, JCKen_US
dc.contributor.authorLai, KNen_US
dc.contributor.authorTang, SCWen_US
dc.date.accessioned2013-08-20T12:21:14Z-
dc.date.available2013-08-20T12:21:14Z-
dc.date.issued2012en_US
dc.identifier.citationKidney Week 2012, San Diego, CA., 30 October-4 November 2012. In Journal of the American Society of Nephrology, 2012, v. 23, p. 955A, abstract no. PUB267en_US
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/186849-
dc.descriptionPublication Only: no. PUB267-
dc.description.abstractBACKGROUND: Formation and accumulation of advanced glycation end products (AGEs) are remarkably accelerated in the diabetic kidney. We recently demonstrated that AGEs stimulated various pro-inflammatory and pro-fibrotic responses in cultured human proximal tubular epithelial cells (PTEC). Bone morphogenetic protein (BMP) 7 has been reported to confer renoprotective effects in a variety of cell types and disease models. However, data is lacking in AGEs-induced renal tubular inflammation. Our present study explored the therapeutic potential of BMP7 on AGEs-induced tubular injury and its possible mechanisms. METHODS: Primary human PTEC were growth-arrested and exposed to glycated human serum albumin (AGE-HSA) with or without recombinant human BMP7 (rhBMP7). Pro-inflammatory chemokines and cytokines were detected at both gene and protein levels by real-time PCR and ELISA, respectively. Inhibitors of different signaling pathways were used (SB203580, PD98059 and PDTC for p38 MAPK, p44/42 MAPK and NF-κB respectively) to study the involvement of these pathways. RESULTS: AGE-HSA induced PTEC expression of pro-inflammatory factors through multiple pathways - IL8 through both p38 and p44/42 MAPK pathways, sICAM-1 through p44/42, and MCP1 through p38 MAPK. Although PDTC suppressed the mRNA and protein expression of IL-6 and TNF-α induced by AGE-HSA, AGE failed to stimulate NF-κB under these experimental conditions, indicating involvement of other pathways. rhBMP7 (5-200 ng/mL) dose-dependently attenuated AGE-HSA (100 ug/mL)-induced expression of sICAM-1, MCP1, IL8, TNF-α and IL6 at both mRNA and protein levels. Moreover, rhBMP7 suppressed phosphorylation of p38, p44/42 which was induced by AGE-HSA. CONCLUSIONS: Our in vitro results demonstrated that BMP7 can attenuate pro-inflammatory responses to AGE stimulation in PTEC via suppression of multiple signaling pathways including p38 and p44/42 MAPK. Its potential application as a therapeutic molecule warrants further investigation.-
dc.languageengen_US
dc.publisherAmerican Society of Nephrology. The Journal's web site is located at https://www.asn-online.org/abstracts/-
dc.relation.ispartofJASN Abstract Supplementen_US
dc.titleAnti-inflammatory effects of BMP7 on AGEs-induced tubular injuryen_US
dc.typeConference_Paperen_US
dc.identifier.emailYiu, WH: whyiu@hku.hken_US
dc.identifier.emailChan, LYY: yychanb@hku.hken_US
dc.identifier.emailLeung, JCK: jckleung@hku.hken_US
dc.identifier.emailLai, KN: knlai@hku.hken_US
dc.identifier.emailTang, SCW: scwtang@hku.hken_US
dc.identifier.authorityLeung, JCK=rp00448en_US
dc.identifier.authorityLai, KN=rp00324en_US
dc.identifier.authorityTang, SCW=rp00480en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros220824en_US
dc.identifier.volume23en_US
dc.identifier.spage955A, abstract no. PUB267en_US
dc.identifier.epage955A, abstract no. PUB267en_US
dc.publisher.placeUnited States-

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