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Article: Disruption of the Smad7 gene promotes renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) in mice

TitleDisruption of the Smad7 gene promotes renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) in mice
Authors
KeywordsRenal fibrosis
Renal inflammation
Smad7
TGF-β signalling
UUO
Issue Date2009
PublisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/
Citation
Nephrology Dialysis Transplantation, 2009, v. 24 n. 5, p. 1443-1454 How to Cite?
AbstractBackground. The present study tested the hypothesis that disruption of Smad7 function may accelerate renal fibrosis and inflammation.Methods. This was investigated in a unilateral ureteral obstruction (UUO) model induced in wild-type (WT) and Smad7ΔE1 mice in which functional Smad7 is disrupted by deleting exon I in the Smad7 gene. Renal fibrosis and inflammation after UUO were examined by histology, real-time PCR, western blot analyses and immunohistochemistry.Results. Seven days after UUO, severe tubulointerstitial fibrosis developed in WT mice as evidenced by a marked increase in α-SMA, collagen I and III extracellular matrix. This was associated with a significant upregulation of renal TGF-β1 and CTGF and activation of Smad23. Interestingly, compared to WT UUO mice, Smad7ΔE1 mice with UUO exhibited a further increase in TGF-βSmad23-dependent renal fibrosis. Moreover, compared to WT UUO mice, deletion of the Smad7 gene also sustained NF-κB activation and thus enhanced further renal inflammation such as macrophage infiltration and upregulation of TNF-α, MCP-1, OPN and ICAM-1.Conclusion. Smad7 is a critical negative regulator of TGF-βSmad23 and NF-κB signalling and plays a negative regulating role in both renal fibrosis and inflammation after UUO. Results from this study further support the notion that Smad7 may be a therapeutic agent for kidney diseases.
Persistent Identifierhttp://hdl.handle.net/10722/59280
ISSN
2015 Impact Factor: 4.085
2015 SCImago Journal Rankings: 1.780
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong Kong (RGC GRF)759206
768207
Funding Information:

We specially thank Dr Fred A. Pereira for the helpful comments and corrections in the manuscript. This work has been supported by grants from Research Grant Council of Hong Kong (RGC GRF 759206 and 768207).

References

 

DC FieldValueLanguage
dc.contributor.authorChung, ACKen_HK
dc.contributor.authorHuang, XRen_HK
dc.contributor.authorZhou, Len_HK
dc.contributor.authorHeuchel, Ren_HK
dc.contributor.authorLai, KNen_HK
dc.contributor.authorLan, HYen_HK
dc.date.accessioned2010-05-31T03:46:54Z-
dc.date.available2010-05-31T03:46:54Z-
dc.date.issued2009en_HK
dc.identifier.citationNephrology Dialysis Transplantation, 2009, v. 24 n. 5, p. 1443-1454en_HK
dc.identifier.issn0931-0509en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59280-
dc.description.abstractBackground. The present study tested the hypothesis that disruption of Smad7 function may accelerate renal fibrosis and inflammation.Methods. This was investigated in a unilateral ureteral obstruction (UUO) model induced in wild-type (WT) and Smad7ΔE1 mice in which functional Smad7 is disrupted by deleting exon I in the Smad7 gene. Renal fibrosis and inflammation after UUO were examined by histology, real-time PCR, western blot analyses and immunohistochemistry.Results. Seven days after UUO, severe tubulointerstitial fibrosis developed in WT mice as evidenced by a marked increase in α-SMA, collagen I and III extracellular matrix. This was associated with a significant upregulation of renal TGF-β1 and CTGF and activation of Smad23. Interestingly, compared to WT UUO mice, Smad7ΔE1 mice with UUO exhibited a further increase in TGF-βSmad23-dependent renal fibrosis. Moreover, compared to WT UUO mice, deletion of the Smad7 gene also sustained NF-κB activation and thus enhanced further renal inflammation such as macrophage infiltration and upregulation of TNF-α, MCP-1, OPN and ICAM-1.Conclusion. Smad7 is a critical negative regulator of TGF-βSmad23 and NF-κB signalling and plays a negative regulating role in both renal fibrosis and inflammation after UUO. Results from this study further support the notion that Smad7 may be a therapeutic agent for kidney diseases.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/en_HK
dc.relation.ispartofNephrology Dialysis Transplantationen_HK
dc.subjectRenal fibrosisen_HK
dc.subjectRenal inflammationen_HK
dc.subjectSmad7en_HK
dc.subjectTGF-β signallingen_HK
dc.subjectUUOen_HK
dc.titleDisruption of the Smad7 gene promotes renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) in miceen_HK
dc.typeArticleen_HK
dc.identifier.emailLai, KN: knlai@hku.hken_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/ndt/gfn699en_HK
dc.identifier.pmid19096081-
dc.identifier.scopuseid_2-s2.0-65249099522en_HK
dc.identifier.hkuros161409en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-65249099522&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume24en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1443en_HK
dc.identifier.epage1454en_HK
dc.identifier.isiWOS:000265275000018-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChung, ACK=7103291604en_HK
dc.identifier.scopusauthoridHuang, XR=7410248090en_HK
dc.identifier.scopusauthoridZhou, L=7404125996en_HK
dc.identifier.scopusauthoridHeuchel, R=6602181532en_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK
dc.identifier.scopusauthoridLan, HY=7102710832en_HK
dc.identifier.citeulike4412238-

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