| First Author | Zhong X | Year | 2013 |
| Journal | Diabetologia | Volume | 56 |
| Issue | 3 | Pages | 663-74 |
| PubMed ID | 23292313 | Mgi Jnum | J:194766 |
| Mgi Id | MGI:5474712 | Doi | 10.1007/s00125-012-2804-x |
| Citation | Zhong X, et al. (2013) miR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes. Diabetologia 56(3):663-74 |
| abstractText | AIMS/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-beta and NF-kappaB signalling pathways. CONCLUSIONS/INTERPRETATION: Inhibition of miR-21 might be an effective therapy for diabetic nephropathy. |
