Your browser doesn't support javascript.
loading
miR-448-3p alleviates diabetic vascular dysfunction by inhibiting endothelial-mesenchymal transition through DPP-4 dysregulation.
Guan, Guo-Ying; Wei, Nan; Song, Tao; Zhao, Chao; Sun, Yang; Pan, Ru-Xin; Zhang, Lu-Lu; Xu, Ying-Ying; Dai, Ya-Mei; Han, Hui.
Afiliação
  • Guan GY; Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Wei N; Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Song T; Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Zhao C; Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Sun Y; Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Pan RX; Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Zhang LL; Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Xu YY; Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Dai YM; Physical Examination Center, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Han H; Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
J Cell Physiol ; 235(12): 10024-10036, 2020 12.
Article em En | MEDLINE | ID: mdl-32542696
Diabetes mellitus (DM) often causes vascular endothelial damage and alters vascular microRNA (miR) expression. miR-448-3p has been reported to be involved in the development of DM, but whether miR-448-3p regulates diabetic vascular endothelial dysfunction remains unclear. To investigate the molecular mechanism of diabetic vascular endothelial dysfunction and the role of miR-448-3p therein, Sprague-Dawley rats were injected with streptozotocin (STZ) to establish diabetic animal model and the rat aortic endothelial cells were treated with high glucose to establish diabetic cell model. For the treatment group, after the induction of diabetes, the miR-448-3p levels in vivo and in vitro were upregulated by adeno-associated virus serotype 2 (AAV2)-miR-448-3p injection and miR-448-3p mimic transfection, respectively. Our results showed that AAV2-miR-448-3p injection alleviated the body weight loss and blood glucose level elevation induced by STZ injection. The miR-448-3p level was significantly decreased and the dipeptidyl peptidase-4 (DPP-4) messenger RNA level was increased in diabetic animal and cell models, which was reversed by miR-448-3p treatment. Moreover, the diabetic rats exhibited endothelial damage and endothelial-mesenchymal transition (EndMT), while AAV2-miR-448-3p injection relieved those situations. In vitro experiments demonstrated that miR-448-3p overexpression in endothelial cells alleviated endothelial damage by inhibiting EndMT through blocking the transforming growth factor-ß/Smad pathway. We further proved that miR-448-3p negatively regulated DPP-4 by binding to its 3'-untranslated region, and DPP-4 overexpression reversed the effect of miR-448-3p overexpression on EndMT. Overall, we conclude that miR-448-3p overexpression inhibits EndMT via targeting DPP-4 and further ameliorates diabetic vascular endothelial dysfunction, indicating that miR-448-3p may serve as a promising therapeutic target for diabetic endothelial dysfunction.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dipeptidil Peptidase 4 / MicroRNAs / Diabetes Mellitus / Angiopatias Diabéticas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: J Cell Physiol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dipeptidil Peptidase 4 / MicroRNAs / Diabetes Mellitus / Angiopatias Diabéticas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: J Cell Physiol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China