Podocyte-specific knockin of PTEN protects kidney from hyperglycemia.
Am J Physiol Renal Physiol
; 314(6): F1096-F1107, 2018 06 01.
Article
em En
| MEDLINE
| ID: mdl-29361670
ABSTRACT
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has proven to be downregulated in podocytes challenged with high glucose (HG), and knockout of PTEN in podocytes aggravated the progression of diabetic kidney disease (DKD). However, whether podocyte-specific knockin of PTEN protects the kidney against hyperglycemia in vivo remains unknown. The inducible podocyte-specific PTEN knockin (PPKI) mice were generated by crossing newly created transgenic loxP-stop- loxP-PTEN mice with podocin-iCreERT2 mice. Diabetes mellitus was induced in mice by intraperitoneal injection of streptozotocin at a dose of 150 mg/kg. In vitro, small interfering RNA and adenovirus interference were used to observe the role of PTEN in HG-treated podocytes. Our data demonstrated that PTEN was markedly reduced in the podocytes of patients with DKD and focal segmental glomerulosclerosis, as well as in those of db/db mice. Interestingly, podocyte-specific knockin of PTEN significantly alleviated albuminuria, mesangial matrix expansion, effacement of podocyte foot processes, and incrassation of glomerular basement membrane in diabetic PPKI mice compared with wild-type diabetic mice, whereas no alteration was observed in the level of blood glucose. The potential renal protection of overexpressed PTEN in podocytes was partly attributed with an improvement in autophagy and motility and the inhibition of apoptosis. Our results showed that podocyte-specific knockin of PTEN protected the kidney against hyperglycemia in vivo , suggesting that targeting PTEN might be a novel and promising therapeutic strategy against DKD.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Glicemia
/
Diabetes Mellitus Experimental
/
Nefropatias Diabéticas
/
Podócitos
/
PTEN Fosfo-Hidrolase
/
Técnicas de Introdução de Genes
/
Hiperglicemia
/
Rim
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article