File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: MiR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes

TitleMiR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes
Authors
KeywordsDiabetic nephropathy
MicroRNA-21
Smad7
TGF-β signalling
Issue Date2013
Citation
Diabetologia, 2013, v. 56, n. 3, p. 663-674 How to Cite?
AbstractAims/hypothesis: As microRNA-21 (miR-21) plays a pathological role in fibrosis, we hypothesised that it may be a therapeutic target for diabetic nephropathy. Methods: Abundance of miR-21 was examined in diabetic kidneys from db/db mice. The therapeutic potential of miR-21 in diabetic kidney injury was examined in db/db mice by an ultrasound-microbubble-mediated miR-21 small hairpin RNA transfer. In addition, the role and mechanisms of miR-21 in diabetic renal injury were examined in vitro under diabetic conditions in rat mesangial and tubular epithelial cell lines by overexpressing or downregulating miR-21. Results: In db/db mice, a mouse model of type 2 diabetes, renal miR-21 at age 20 weeks was increased twofold compared with db/m + mice at the same age, and this increase was associated with the development of microalbuminuria and renal fibrosis and inflammation. More importantly, gene transfer of miR-21 knockdown plasmids into the diabetic kidneys of db/db mice at age 10 weeks significantly ameliorated microalbuminuria and renal fibrosis and inflammation at age 20 weeks, revealing a therapeutic potential for diabetic nephropathy by targeting miR-21. Overexpression of miR-21 in kidney cells enhanced, but knockdown of miR-21 suppressed, high-glucose-induced production of fibrotic and inflammatory markers. Targeting Smad7 may be a mechanism by which miR-21 regulates renal injury because knockdown of renal miR-21 restored Smad7 levels and suppressed activation of the TGF-β and NF-κB signalling pathways. Conclusions/interpretation: Inhibition of miR-21 might be an effective therapy for diabetic nephropathy. © 2012 Springer-Verlag Berlin Heidelberg.
Persistent Identifierhttp://hdl.handle.net/10722/200135
ISSN
2015 Impact Factor: 6.206
2015 SCImago Journal Rankings: 3.528
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhong, Xiang-
dc.contributor.authorChung, Arthur Chi Kong-
dc.contributor.authorChen, Hai-Yong-
dc.contributor.authorDong, Yuan-
dc.contributor.authorMeng, Xiaoming-
dc.contributor.authorLi, Rong-
dc.contributor.authorYang, Weiqin-
dc.contributor.authorHou, F. F.-
dc.contributor.authorLan, Huiyao-
dc.date.accessioned2014-07-26T23:11:10Z-
dc.date.available2014-07-26T23:11:10Z-
dc.date.issued2013-
dc.identifier.citationDiabetologia, 2013, v. 56, n. 3, p. 663-674-
dc.identifier.issn0012-186X-
dc.identifier.urihttp://hdl.handle.net/10722/200135-
dc.description.abstractAims/hypothesis: As microRNA-21 (miR-21) plays a pathological role in fibrosis, we hypothesised that it may be a therapeutic target for diabetic nephropathy. Methods: Abundance of miR-21 was examined in diabetic kidneys from db/db mice. The therapeutic potential of miR-21 in diabetic kidney injury was examined in db/db mice by an ultrasound-microbubble-mediated miR-21 small hairpin RNA transfer. In addition, the role and mechanisms of miR-21 in diabetic renal injury were examined in vitro under diabetic conditions in rat mesangial and tubular epithelial cell lines by overexpressing or downregulating miR-21. Results: In db/db mice, a mouse model of type 2 diabetes, renal miR-21 at age 20 weeks was increased twofold compared with db/m + mice at the same age, and this increase was associated with the development of microalbuminuria and renal fibrosis and inflammation. More importantly, gene transfer of miR-21 knockdown plasmids into the diabetic kidneys of db/db mice at age 10 weeks significantly ameliorated microalbuminuria and renal fibrosis and inflammation at age 20 weeks, revealing a therapeutic potential for diabetic nephropathy by targeting miR-21. Overexpression of miR-21 in kidney cells enhanced, but knockdown of miR-21 suppressed, high-glucose-induced production of fibrotic and inflammatory markers. Targeting Smad7 may be a mechanism by which miR-21 regulates renal injury because knockdown of renal miR-21 restored Smad7 levels and suppressed activation of the TGF-β and NF-κB signalling pathways. Conclusions/interpretation: Inhibition of miR-21 might be an effective therapy for diabetic nephropathy. © 2012 Springer-Verlag Berlin Heidelberg.-
dc.languageeng-
dc.relation.ispartofDiabetologia-
dc.subjectDiabetic nephropathy-
dc.subjectMicroRNA-21-
dc.subjectSmad7-
dc.subjectTGF-β signalling-
dc.titleMiR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s00125-012-2804-x-
dc.identifier.pmid23292313-
dc.identifier.scopuseid_2-s2.0-84878269299-
dc.identifier.hkuros232087-
dc.identifier.volume56-
dc.identifier.issue3-
dc.identifier.spage663-
dc.identifier.epage674-
dc.identifier.eissn1432-0428-
dc.identifier.isiWOS:000314531700026-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats