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Diabetologia

Erschienen in:

01.05.2014 | Article

miR-195 regulates SIRT1-mediated changes in diabetic retinopathy

verfasst von: Rokhsana Mortuza, Biao Feng, Subrata Chakrabarti

Erschienen in: Diabetologia | Ausgabe 5/2014

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Abstract

Aims/hypothesis

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/interpretation

These studies identified a novel mechanism whereby miR-195 regulates SIRT1-mediated tissue damage in diabetic retinopathy.

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Titel: miR-195 regulates SIRT1-mediated changes in diabetic retinopathy
verfasst von: Rokhsana Mortuza
Biao Feng
Subrata Chakrabarti
Publikationsdatum: 01.05.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 5/2014
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-014-3197-9

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