Expert opinion on therapeutic targets · 2022
The mineralocorticoid receptor signal could be a new molecular target for the treatment of diabetic retinal complication.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Ohashi Kennosuke, Hayashi Takeshi, Utsunomiya Kazunori, Nishimura Rimei
Аннотация
BACKGROUND: Activation of the mineralocorticoid receptor (MR) is involved in the pathophysiology of diabetic vascular complications. In recent years, it has been indicated that the MR expressed in retinal Müller cells plays an important role in regulating the potassium and water balance in the retina. Therefore, it has also been speculated that abnormal MR signaling contributes to edematous diseases of the retina.
RESEARCH DESIGN AND METHODS: We examined the effect of high-glucose conditions on MR protein and mRNA levels in human retinal Müller cells and changes in cell size in vitro. We also investigated MR transcriptional activity and signaling in high-glucose conditions.
RESULTS: The MR protein increased by 2.2-fold with high-glucose treatment. Additionally, high-glucose treatment induced Müller cell swelling. Aldosterone-induced MR transcriptional activity was enhanced in high-glucose conditions, resulting in the upregulation of αENaC, AQP4, and Kir4.1 mRNA. Treatment with an MR antagonist led to the suppression of aldosterone-induced cell swelling, MR transcriptional activity, and upregulation of the target genes in high-glucose conditions.
CONCLUSIONS: High glucose induces Müller cell swelling through activation of MR signaling, which could be associated with aggravation of macular edema. Thus, Müller cell swelling and diabetic macular edema may represent a target for treatment with MR antagonists.
RESEARCH DESIGN AND METHODS: We examined the effect of high-glucose conditions on MR protein and mRNA levels in human retinal Müller cells and changes in cell size in vitro. We also investigated MR transcriptional activity and signaling in high-glucose conditions.
RESULTS: The MR protein increased by 2.2-fold with high-glucose treatment. Additionally, high-glucose treatment induced Müller cell swelling. Aldosterone-induced MR transcriptional activity was enhanced in high-glucose conditions, resulting in the upregulation of αENaC, AQP4, and Kir4.1 mRNA. Treatment with an MR antagonist led to the suppression of aldosterone-induced cell swelling, MR transcriptional activity, and upregulation of the target genes in high-glucose conditions.
CONCLUSIONS: High glucose induces Müller cell swelling through activation of MR signaling, which could be associated with aggravation of macular edema. Thus, Müller cell swelling and diabetic macular edema may represent a target for treatment with MR antagonists.