Involvement of miR-451 in the regulation of glomerular hypertrophy in db/db mouse with diabetic nephropathy at early stage

Abstract:

Objective：To observe the effect of miR-451 on glomerular morphological changes in diabetic nephmpathy（DN） of type 2 diabetic db/db mice and to explore the role of miR-451 in pathogenesis of early DN. Methods：Thirty-two 7-week-old db/db and normal db/m male mice were divided into miR-451 group，empty plasmid group，untreated group and normal control group. After in－traperitoneal injection of plasmid for two weeks，the glomerular morphological changes were observed under the light microscope. Also，the expression of miR-451 was tested by real-time PCR and the tyrosine3-monooxy-genase/tryptophan 5-monooxygenase activation protein（Ywhaz），p38MAPK and MAPK kinase 3（MKK3） protein levels were examined by Western blot and immunofluorescence. Results：Elevation of urinary albumin excretion rate（UAE） was shown in the untreated group of 7-week-old db/db mice，suggesting that the 7-week-old db/db mice had the features similar to the diabetic nephropathy at early stage. Then plasmid injection ex－periment was executed on mice for two weeks. Real-time RT-PCR results showed that miR-451 was 1.79 folds high in miR-451 group than in empty plasmid group（P=0.002）. Also，glo-meruli acreage was smaller in miR-451-treated group than in the empty plasmid and untreated groups（P=0.000）. Moreover，Western blot and immunofluorescence results demonstrated that Ywhaz，p38MAPK and MKK3 proteins were reduced in miR-451 group（P=0.000）. Conclusion：miR-451 can repress glomerular hypertrophy by targeting Ywhaz gene and affecting MAPK signal pathway. Therefore，miR-451 might play an important role in the pathogenesis of DN.