title: miR-195 regulates SIRT1-mediated changes in diabetic retinopathy.
abstract: OBJECTIVE
  Endothelial cell (EC) damage is a key mechanism causing retinal microvascular injury in diabetes. Several microRNAs (miRNAs) have been found to regulate sirtuin 1 (SIRT1, which is involved in regulation of the cell cycle, survival and metabolism) in various tissues and disease states, but no studies have been conducted on the role of miRNA in regulation of SIRT1 in diabetic retinopathy. Here we investigated the effect of miRNA-195 (miR-195), a SIRT1-targeting miRNA, on the development of diabetes-induced changes in ECs and retina.
  
  
  METHODS
  The level of miR-195 was measured in human retinal and dermal microvascular ECs (HRECs, HMECs) following exposure to 25 mmol/l glucose (high glucose, HG) and 5 mmol/l glucose (normal glucose, NG). SIRT1 and fibronectin levels were examined following transfection with miR-195 mimic or antagomir or forced expression of SIRT1. Retinal tissues from diabetic rats were similarly studied following intravitreal injection of an miR-195 antagomir or mimic. In situ hybridisation was used to localise retinal miR-195.
  
  
  RESULTS
  HG caused increased miR-195 levels and decreased SIRT1 expression (compared with NG) in both HRECs and HMECs. Transfection with miR-195 antagomir and forced expression of SIRT1 prevented such changes, whereas transfection with miR-195 mimic produced HG-like effects. A luciferase assay confirmed the binding of miR-195 to the 3' untranslated region of SIRT1. miR-195 expression was upregulated in retinas of diabetic rats and intravitreal injection of miR-195 antagomir ameliorated levels of SIRT1.
  
  
  CONCLUSIONS
  These studies identified a novel mechanism whereby miR-195 regulates SIRT1-mediated tissue damage in diabetic retinopathy.
authors.affiliation: Department of Pathology, Schulich School of Medicine and Dentistry, Western University, DSB - 4033, London, ON, Canada, N6A 5C1.
authors.forename: Rokhsana
authors.initials: R
authors.lastname: Mortuza
authors.forename: Biao
authors.initials: B
authors.lastname: Feng
authors.forename: Subrata
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D020413:3' Untranslated Regions; D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003920:Diabetes Mellitus / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism*; D012867:Skin / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D005353:Fibronectins; C552722:MIRN195 microRNA, human; C584139:MIRN195 microRNA, rat; D035683:MicroRNAs; C447939:SIRT1 protein, human; C488368:Sirt1 protein, rat; D056564:Sirtuin 1