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Article: Smad7 inhibits AngII-mediated hypertensive nephropathy in a mouse model of hypertension

TitleSmad7 inhibits AngII-mediated hypertensive nephropathy in a mouse model of hypertension
Authors
KeywordsNuclear factor κB (NF-κB)
Smad3
Smad7
Sp1
Hypertensive nephropathy
MiR-29
Issue Date2014
Citation
Clinical Science, 2014, v. 127, n. 3, p. 195-208 How to Cite?
AbstractThe TGFβ (transforming growth factor β)/SMAD and NF-κB (nuclear factor κB) signalling pathways play a key role in hypertensive nephropathy. The present study examined whether targeting these pathways by SMAD7, a downstream inhibitor of both pathways, blocks AngII (angiotensin II)-induced hypertensive kidney disease in mice. A doxycycline-inducible SMAD7-expressing plasmid was delivered into the kidney by a non-invasive ultrasound-microbubble technique before and after AngII infusion. Results showed that pre-treatment with SMAD7 prevented AngII-induced progressive renal injury by inhibiting an increase in proteinuria and serum creatinine while improving the glomerular filtration rate. Similarly, treatment with SMAD7 in the established hypertensive nephropathy at day 14 after AngII infusion halted the progressive renal injury. These preventive and therapeutic effects of SMAD7 on hypertensive kidney injury were associated with inhibition of AngII-induced up-regulation of SMURF2 (SMAD-specific E3 ubiquitin protein ligase 2) and Sp1 (specificity protein 1), blockade of TGFβ/Smad3-mediated renal fibrosis and suppression of NF-κB-driven renal inflammation. Moreover, overexpression of SMAD7 also prevented AngII-induced loss of renal miR-29b, an miRNA with an inhibitory role in both TGFβ/Smad3 and NF-κB pathways. In conclusion, SMAD7 may be a therapeutic agent for AngII-mediated hypertensive nephropathy. Inhibition of the Sp1/SMAD3/NF-κB/miR-29b regulatory network may be a mechanism by which SMAD7 inhibits hypertensive nephropathy. © 2014 Biochemical Society.
Persistent Identifierhttp://hdl.handle.net/10722/200150
ISSN
2015 Impact Factor: 4.996
2015 SCImago Journal Rankings: 2.427
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, Guanxian-
dc.contributor.authorLi, Youqi-
dc.contributor.authorHuang, Xiaoru-
dc.contributor.authorWei, Lihua-
dc.contributor.authorZhang, Yang-
dc.contributor.authorFeng, Min-
dc.contributor.authorMeng, Xiaoming-
dc.contributor.authorChen, Hai-Yong-
dc.contributor.authorShi, Yongjun-
dc.contributor.authorLan, Huiyao-
dc.date.accessioned2014-07-26T23:11:11Z-
dc.date.available2014-07-26T23:11:11Z-
dc.date.issued2014-
dc.identifier.citationClinical Science, 2014, v. 127, n. 3, p. 195-208-
dc.identifier.issn0143-5221-
dc.identifier.urihttp://hdl.handle.net/10722/200150-
dc.description.abstractThe TGFβ (transforming growth factor β)/SMAD and NF-κB (nuclear factor κB) signalling pathways play a key role in hypertensive nephropathy. The present study examined whether targeting these pathways by SMAD7, a downstream inhibitor of both pathways, blocks AngII (angiotensin II)-induced hypertensive kidney disease in mice. A doxycycline-inducible SMAD7-expressing plasmid was delivered into the kidney by a non-invasive ultrasound-microbubble technique before and after AngII infusion. Results showed that pre-treatment with SMAD7 prevented AngII-induced progressive renal injury by inhibiting an increase in proteinuria and serum creatinine while improving the glomerular filtration rate. Similarly, treatment with SMAD7 in the established hypertensive nephropathy at day 14 after AngII infusion halted the progressive renal injury. These preventive and therapeutic effects of SMAD7 on hypertensive kidney injury were associated with inhibition of AngII-induced up-regulation of SMURF2 (SMAD-specific E3 ubiquitin protein ligase 2) and Sp1 (specificity protein 1), blockade of TGFβ/Smad3-mediated renal fibrosis and suppression of NF-κB-driven renal inflammation. Moreover, overexpression of SMAD7 also prevented AngII-induced loss of renal miR-29b, an miRNA with an inhibitory role in both TGFβ/Smad3 and NF-κB pathways. In conclusion, SMAD7 may be a therapeutic agent for AngII-mediated hypertensive nephropathy. Inhibition of the Sp1/SMAD3/NF-κB/miR-29b regulatory network may be a mechanism by which SMAD7 inhibits hypertensive nephropathy. © 2014 Biochemical Society.-
dc.languageeng-
dc.relation.ispartofClinical Science-
dc.subjectNuclear factor κB (NF-κB)-
dc.subjectSmad3-
dc.subjectSmad7-
dc.subjectSp1-
dc.subjectHypertensive nephropathy-
dc.subjectMiR-29-
dc.titleSmad7 inhibits AngII-mediated hypertensive nephropathy in a mouse model of hypertension-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1042/CS20130706-
dc.identifier.pmid24511990-
dc.identifier.scopuseid_2-s2.0-84898772136-
dc.identifier.hkuros232083-
dc.identifier.volume127-
dc.identifier.issue3-
dc.identifier.spage195-
dc.identifier.epage208-
dc.identifier.isiWOS:000339225900006-
dc.identifier.f1000718273208-

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