Por favor, use este identificador para citar o enlazar este ítem:
https://doi.org/10.14670/HH-18-358
Twittear
Título: | Death-associated protein kinase 1 correlates with podocyte apoptosis and renal damage and can be mediated by miR-361 |
Fecha de publicación: | 2021 |
Editorial: | Universidad de Murcia, Departamento de Biologia Celular e Histiologia |
Cita bibliográfica: | Histology and Histopathology Vol. 36, nº11 (2021) |
ISSN: | 0213-3911 1699-5848 |
Materias relacionadas: | CDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología |
Palabras clave: | miR-361 DAPK1 Podocyte High glucose Apoptosis |
Resumen: | Background. Herein, we aimed to determine whether DAPK1 and its post-transcriptional regulator miR-361 were implicated in high glucose (HG)-induced podocyte injury and renal damage in db/db mice. Materials and methods. Podocytes were incubated with normal glucose (NG; 5 mM) or HG (30 mM). Podocyte apoptosis was evaluated using TUNEL staining. Lentiviral-delivered specific short hairpin RNA (shRNA) was designed to silence DAPK1 expression in podocytes. miR-361 agomir was administrated by tail intravenous injection in db/db diabetic mice to investigate the renoprotection of miR-361 in vivo. Results. Exposure of podocytes to HG led to a significant increase in DAPK1 mRNA and protein levels and a decrease in miR-361 expression levels. Knockdown of DAPK1 attenuated HG-triggered growth inhibition, apoptosis, DNA damage and cell membrane damage in podocytes. Mechanically, DAPK1 was a direct target of miR-361. Transfection with miR-361 mimics into podocytes resulted in a significant decrease in the DAPK1 protein expression level. In addition, HGinduced the up-regulation of the DAPK1 protein expression level in podocytes was restrained by miR-361 mimics transfection. Intriguingly, overexpression of DAPK1 in HG-stimulated podocytes muted miR-361- mediated cytoprotection, including anti-apoptosis, resistance to DNA and membrane damage. In vivo, overexpression of miR-361 protected against hyperglycemia-induced podocyte loss, tubular atrophy and interstitial fibrosis in the kidney of db/db mice. Moreover, overexpression of miR-361 inhibited the protein expression of DAPK1 in the kidney of db/db mice. Conclusion. Our research presented a novel mechanism of HG-induced podocyte damage or renal lesion, supporting the miR-361/DAPK1 signaling pathway that could be used as a potential therapeutic target for the treatment of DN. |
Autor/es principal/es: | Wu, Guang-jun Zhao, Hong-biao Zhang, Xiao-wei |
URI: | http://hdl.handle.net/10201/127986 |
DOI: | https://doi.org/10.14670/HH-18-358 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 13 |
Derechos: | info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
Aparece en las colecciones: | Vol.36,nº11 (2021) |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
Wu-36-1155-1167-2021.pdf | 8,47 MB | Adobe PDF | Visualizar/Abrir |
Este ítem está sujeto a una licencia Creative Commons Licencia Creative Commons