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Manuela Bartoli, Folami Lamoke, Chaunte' Stampley, Anna Lisa Montemari, AnnaMaria Maraschi, Ruth B. Caldwell; Microrna21 Is Up-regulated In The Ischemic Retina In A Stat3-dependent Manner. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3971.
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© ARVO (1962-2015); The Authors (2016-present)
MicroRNA 21 (mir21) has been recently shown to be involved in angiogenic processes by promoting matrix metalloproteinases (MMPs) activity. We have previously shown that the transcription factor signal transducer and activator of transcription 3 (STAT3) is activated in the ischemic retina where it regulates VEGF expression and activity. Recent studies have suggested that STAT3 may control mir21 expression, therefore, in the present study we investigated the expression pattern of mir21 in the ischemic retina and characterized STAT3 role in its induction.
The mouse model of oxygen induced retinopathy (OIR) was used to assess levels of mir21 using qRT-PCR. Retinal endothelial cells (RECs) were transfected with specific siRNAs for STAT3 or not targeted siRNAs (NT-siRNA) and then exposed to hypoxic conditions (pO2=2%). Western blotting analysis was conducted to measure phosphorylation of STAT3 at tyrosine 705 (PYSTAT3).
Mir21 expression was progressively increased in RNA extracts of OIR mice retina and showed maximal expression at 14 and 17 days postnatal (OIRP14 and OIRP17 respectively) as compared to age-matched murine retinas (P14 and P17). This effect correlated with increased levels of PYSTAT3, the transcriptionally active form of STAT3. Mir21 was also up-regulated in RECs exposed to hypoxic conditions (at 6 and 12 hours) and inhibition of STAT3 activation by transfection of RECs with STAT3 siRNA, but not with NT-siRNA, resulted in blockade of hypoxia-induced mir21 expression.
Our results suggest that mir21 is up-regulated in the ischemic retina and in RECs exposed to hypoxic conditions. In addition, hypoxia-induced mir21 in RECs is STAT3 dependent. These results, while disclosing a new function for STAT3 in the ischemic retina, suggest a potential role for mir21 in sustaining retinal neovascularization.
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