Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice.
Physiol Rep
; 7(13): e14141, 2019 08.
Article
en En
| MEDLINE
| ID: mdl-31250538
Metformin is today the first choice treatment for type-2 diabetes, but has also protective effects in several renal disease models. Previously, we have demonstrated that the protective effects in response to unilateral ureteral obstruction (UUO) are independent of organic cation transporters (OCTs), the transporters responsible for the metformin uptake into the renal cells. The mechanisms behind the renoprotective effects are incompletely understood, but our previous results indicate that the renoprotective effects at least partly could be dependent on actions of metformin outside the renal cells. In this study, we investigate whether the renoprotective effects of metformin can be mediated via systemic immunomodulatory actions. We demonstrated that metformin can affect the immune system in the kidney as well as in the peripheral blood and spleen following UUO. UUO kidneys showed infiltration of immune cells including monocytes, B cells, and T cells, but metformin limited infiltration of all cell types. UUO animals had increased spleen sizes, but this increase was attenuated by metformin. Metformin treatment surprisingly resulted in a higher proportion of monocytes with infiltratory capacity 7 days after UUO. Other studies have suggested that metformin regulates monocyte maturation through signal transducer and activator of transcription 3 (STAT3) activation, as also indicated by our results. In conclusion, our results demonstrate that metformin limits the infiltration of immune cells into the kidney, as well as modulates immune cell composition at a systemic level.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Obstrucción Ureteral
/
Linfocitos B
/
Monocitos
/
Linfocitos T
/
Movimiento Celular
/
Riñón
/
Metformina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Physiol Rep
Año:
2019
Tipo del documento:
Article
País de afiliación:
Dinamarca
Pais de publicación:
Estados Unidos