12-HETE activates Müller glial cells: The potential role of GPR31 and miR-29

Diabetic retinopathy (DR) is a neurovascular complication of diabetes, driven by an intricate network of cellular and molecular mechanisms. This study sought to explore the mechanisms by investigating the role of 12-hydroxyeicosatetraenoic acid (12-HETE), its receptor GPR31, and microRNA (miR-29) in...

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Published in:Prostaglandins & other lipid mediators 2024-04, Vol.171, p.106805-106805, Article 106805
Main Authors: Moustafa, Mohamed, Khalil, Abraham, Darwish, Noureldien H.E., Zhang, Dao-Qi, Tawfik, Amany, Al-Shabrawey, Mohamed
Format: Article
Language:English
Subjects:
12-HETE
12/15-lipoxygenase
Diabetic Retinopathy
GPR31
MiR-29
Müller glial cells
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Summary:Diabetic retinopathy (DR) is a neurovascular complication of diabetes, driven by an intricate network of cellular and molecular mechanisms. This study sought to explore the mechanisms by investigating the role of 12-hydroxyeicosatetraenoic acid (12-HETE), its receptor GPR31, and microRNA (miR-29) in the context of DR, specifically focusing on their impact on Müller glial cells. We found that 12-HETE activates Müller cells (MCs), elevates glutamate production, and induces inflammatory and oxidative responses, all of which are instrumental in DR progression. The expression of GPR31, the receptor for 12-HETE, was prominently found in the retina, especially in MCs and retinal ganglion cells, and was upregulated in diabetes. Interestingly, miR29 showed potential as a protective agent, mitigating the harmful effects of 12-HETE by attenuating inflammation and oxidative stress, and restoring the expression of pigment epithelium-derived factor (PEDF). Our results underline the central role of 12-HETE in DR progression through activation of a neurovascular toxic pathway in MCs and illuminate the protective capabilities of miR-29, highlighting both as promising therapeutic targets for the management of DR. •12-HETE via GPR31 triggers glutamatergic, inflammatory and oxidative responses in Müller cells.•Diabetes upregulates 12-HETE receptor, GPR31 in mouse retina.•miR29 may counter 12-HETE's pro-inflammatory and oxidative effects in Müller cells.•The 12-HETE/GPR31/miR29 loop is a potential target for treating diabetic retinopathy.
ISSN:1098-8823
DOI:10.1016/j.prostaglandins.2023.106805