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The MicroRNA-21 signaling pathway is involved in prorenin receptor (PRR) -induced VEGF expression in ARPE-19 cells under a hyperglycemic condition.

ABSTRACT: MicroRNAs (miRNAs/miRs) are involved in a large number of biological functions and diseases, such as cancer, cardiovascular diseases, and diabetes. MiR-21 has been reported to target Sprouty homolog 1 (SPRY1), SMAD7, and PTEN. In this study, we examined the underlying role of miR-21 in the regulation of prorenin receptor (PRR)-mediated induction of vascular endothelial growth factor (VEGF) expression via targeting SMAD7, SPRY1, and PTEN in a hyperglycemic condition.PRR-mediated induction of VEGF under a hyperglycemic condition (high glucose, 33mM) was studied by treating ARPE-19 cells with perindopril (10 µmol/l), which inhibits angiotensin II-mediated signaling. ARPE-19 cells exposed to normal glucose (NG, 5.5 mM) were considered as the control. To examine the role of miR-21 in the regulation of SPRY1, SMAD7, PTEN, and VEGF, ARPE-19 cells cultured in NG or high glucose were transfected with scramble negative control (Scr), a miR-21 mimic, or a miR-21 antagomir. To investigate the role of PRR and the small GTP-binding protein RAC1 in the regulation of miR-21, the expression of PRR and RAC1 was silenced by transfecting ARPE-19 cells with their corresponding siRNAs.Compared with the NG control, high glucose significantly induced the expression of PRR, VEGF, VEGFR2, and miR-21 but significantly suppressed the expression of SPRY1, SMAD7, and PTEN at the transcript and protein levels. In contrast, silencing the expression of PRR significantly abolished the high glucose-induced expression of VEGF, VEGFR2, and miR-21. Knockdown of RAC1 significantly attenuated the high glucose-induced expression of LOX, CTGF, and miR-21, suggesting that PRR and RAC1 are involved in the CTGF/LOX-mediated regulation of miR-21. Furthermore, high glucose dramatically increased the levels of pERK (p44), hypoxia-inducible factor (HIF-1?), and VEGF. However, this effect was antagonized by the miR-21 antagomir, indicative of the involvement of high glucose-induced miR-21 in the regulation of VEGF through ERK signaling.Our findings, for the first time, showed that the pleiotropic action of miR-21 induced the expression of pERK, HIF-1?, and VEGF in the high glucose condition by simultaneously targeting SPRY1, SMAD7, and PTEN in ARPE-19 cells. Therefore, miR-21 may serve as a potential therapeutic target for diabetes-induced retinal pathology.

SUBMITTER: Haque R

PROVIDER: S-EPMC5398881 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The MicroRNA-21 signaling pathway is involved in prorenin receptor (PRR) -induced VEGF expression in ARPE-19 cells under a hyperglycemic condition.

Haque Rashidul R Iuvone P Michael PM He Li L Choi Kimberly Su Chung KSC Ngo Ashley A Gokhale Samantha S Aseem Madiha M Park Daniel D

Molecular vision 20170414

<h4>Purpose</h4>MicroRNAs (miRNAs/miRs) are involved in a large number of biological functions and diseases, such as cancer, cardiovascular diseases, and diabetes. MiR-21 has been reported to target Sprouty homolog 1 (SPRY1), SMAD7, and PTEN. In this study, we examined the underlying role of miR-21 in the regulation of prorenin receptor (PRR)-mediated induction of vascular endothelial growth factor (VEGF) expression via targeting SMAD7, SPRY1, and PTEN in a hyperglycemic condition.<h4>Methods</h ...[more]

PMID: 28465657

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The MicroRNA-21 signaling pathway is involved in prorenin receptor (PRR) -induced VEGF expression in ARPE-19 cells under a hyperglycemic condition.

Publications

The MicroRNA-21 signaling pathway is involved in prorenin receptor (PRR) -induced VEGF expression in ARPE-19 cells under a hyperglycemic condition.

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