Cargando…
Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice
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),...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597795/ https://www.ncbi.nlm.nih.gov/pubmed/31250538 http://dx.doi.org/10.14814/phy2.14141 |
_version_ | 1783430652668936192 |
---|---|
author | Christensen, Michael Nørgård, Mikkel Ø. Jensen, Michael S. Møller, Bjarne K. Nørregaard, Rikke |
author_facet | Christensen, Michael Nørgård, Mikkel Ø. Jensen, Michael S. Møller, Bjarne K. Nørregaard, Rikke |
author_sort | Christensen, Michael |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6597795 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65977952019-07-11 Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice Christensen, Michael Nørgård, Mikkel Ø. Jensen, Michael S. Møller, Bjarne K. Nørregaard, Rikke Physiol Rep Original Research 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. John Wiley and Sons Inc. 2019-06-27 /pmc/articles/PMC6597795/ /pubmed/31250538 http://dx.doi.org/10.14814/phy2.14141 Text en © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Christensen, Michael Nørgård, Mikkel Ø. Jensen, Michael S. Møller, Bjarne K. Nørregaard, Rikke Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice |
title | Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice |
title_full | Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice |
title_fullStr | Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice |
title_full_unstemmed | Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice |
title_short | Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice |
title_sort | metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597795/ https://www.ncbi.nlm.nih.gov/pubmed/31250538 http://dx.doi.org/10.14814/phy2.14141 |
work_keys_str_mv | AT christensenmichael metforminmodulatesimmunecellinfiltrationintothekidneyduringunilateralureteralobstructioninmice AT nørgardmikkelø metforminmodulatesimmunecellinfiltrationintothekidneyduringunilateralureteralobstructioninmice AT jensenmichaels metforminmodulatesimmunecellinfiltrationintothekidneyduringunilateralureteralobstructioninmice AT møllerbjarnek metforminmodulatesimmunecellinfiltrationintothekidneyduringunilateralureteralobstructioninmice AT nørregaardrikke metforminmodulatesimmunecellinfiltrationintothekidneyduringunilateralureteralobstructioninmice |