title: Abated microRNA-195 expression protected mesangial cells from apoptosis in early diabetic renal injury in mice.
abstract: BACKGROUND
  MicroRNAs are a class of highly conserved, small, noncoding RNAs that tailor gene expression mainly at the posttranscriptional level. The aim of the present study was to investigate the renal expression profiles of microRNAs and their potential involvement in early diabetic nephropathy.
  
  
  METHODS
  Diabetic models were induced with streptozotocin in DBA/2 mice. MicroRNAs were detected by microarray and subjected to bioinformatics analyses. Real-time PCR and Western blots were performed. The relationships between pathological changes and microRNA expression were evaluated by linear regression analysis. Apoptosis and proliferation of cultured mesangial cells treated with microRNA inhibitor were determined by flow cytometry and MTT assay, respectively.
  
  
  RESULTS
  Nine microRNAs, including miR-1187, miR-320, miR-214, miR-34a, miR-762, miR-466f, miR-720, miR-744 and miR-1937b, were increased significantly. Another 9 microRNAs, including miR-1907, miR-195, miR-568, miR-26b, miR-703, miR-1196, miR-194, miR-805 and miR-192, were decreased remarkably in diabetic mice. The levels of microRNA repressing BCL2 decreased. Accordingly, BCL2 levels were found elevated and caspase-3 and caspase-8 levels decreased in the diabetic group. MicroRNA-195 expression was negatively related to glomeruli diameter, mesangial score and extracellular matrix (ECM) accumulation. Moreover, the microRNA-195 inhibitor protected mesangial cells from apoptosis and promoted the cellular proliferation in vitro.
  
  
  CONCLUSIONS
  These results demonstrated that the abated microRNA-195 expression protected mesangial cells from apoptosis, suggesting that the antiapoptosis in a microRNA-regulated manner may play an important role in the early stages of diabetic nephropathy.
authors: Department of Nephrology and Rheumatology, Shanghai No. 6 Hospital, Shanghai Jiao Tong University, Shanghai, PR China.
authors: Yu Q
authors: YQ
authors: Chen
authors: Xiao X
authors: XX
authors: Wang
authors: Xing M
authors: XM
authors: Yao
authors: Dong L
authors: DL
authors: Zhang
authors: Xu F
authors: XF
authors: Yang
authors: Shou F
authors: SF
authors: Tian
authors: Nian S
authors: NS
authors: Wang
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D019295:Computational Biology; D019610:Cytoprotection; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016376:Oligonucleotides, Antisense / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D015415:Biomarkers; C569389:MIRN195a microRNA, mouse; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; D053148:Caspase 3; D053181:Caspase 8