Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular Filtration
Hyperglycemic conditions (HG), at early stages of diabetic nephropathy (DN), cause a decrease in podocyte numbers and an aberration of their function as key cells for glomerular plasma filtration. Klotho protein was shown to overcome some negative effects of hyperglycemia. Klotho is also a corecepto...
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doaj-dbcf4d70036b4d93911ff9d34cb48a8c2021-08-06T15:24:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-01227867786710.3390/ijms22157867Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular FiltrationMarlena Typiak0Tomasz Kulesza1Patrycja Rachubik2Dorota Rogacka3Irena Audzeyenka4Stefan Angielski5Moin A. Saleem6Agnieszka Piwkowska7Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Wita Stwosza 63, 80-308 Gdansk, PolandLaboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Wita Stwosza 63, 80-308 Gdansk, PolandLaboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Wita Stwosza 63, 80-308 Gdansk, PolandLaboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Wita Stwosza 63, 80-308 Gdansk, PolandLaboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Wita Stwosza 63, 80-308 Gdansk, PolandLaboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Wita Stwosza 63, 80-308 Gdansk, PolandBristol Renal, Dorothy Hodgkin Building, University of Bristol, Bristol BS1 3NY, UKLaboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Wita Stwosza 63, 80-308 Gdansk, PolandHyperglycemic conditions (HG), at early stages of diabetic nephropathy (DN), cause a decrease in podocyte numbers and an aberration of their function as key cells for glomerular plasma filtration. Klotho protein was shown to overcome some negative effects of hyperglycemia. Klotho is also a coreceptor for fibroblast growth factor receptors (FGFRs), the signaling of which, together with a proper rate of glycolysis in podocytes, is needed for a proper function of the glomerular filtration barrier. Therefore, we measured levels of Klotho in renal tissue, serum, and urine shortly after DN induction. We investigated whether it influences levels of FGFRs, rates of glycolysis in podocytes, and albumin permeability. During hyperglycemia, the level of membrane-bound Klotho in renal tissue decreased, with an increase in the shedding of soluble Klotho, its higher presence in serum, and lower urinary excretion. The addition of Klotho increased FGFR levels, especially FGFR1/FGFR2, after their HG-induced decrease. Klotho also increased levels of glycolytic parameters of podocytes, and decreased podocytic and glomerular albumin permeability in HG. Thus, we found that the decrease in the urinary excretion of Klotho might be an early biomarker of DN and that Klotho administration may have several beneficial effects on renal function in DN.https://www.mdpi.com/1422-0067/22/15/7867Klotho proteindiabetes mellitusdiabetic nephropathyhyperglycemiafibroblast growth factor receptors |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marlena Typiak Tomasz Kulesza Patrycja Rachubik Dorota Rogacka Irena Audzeyenka Stefan Angielski Moin A. Saleem Agnieszka Piwkowska |
spellingShingle |
Marlena Typiak Tomasz Kulesza Patrycja Rachubik Dorota Rogacka Irena Audzeyenka Stefan Angielski Moin A. Saleem Agnieszka Piwkowska Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular Filtration International Journal of Molecular Sciences Klotho protein diabetes mellitus diabetic nephropathy hyperglycemia fibroblast growth factor receptors |
author_facet |
Marlena Typiak Tomasz Kulesza Patrycja Rachubik Dorota Rogacka Irena Audzeyenka Stefan Angielski Moin A. Saleem Agnieszka Piwkowska |
author_sort |
Marlena Typiak |
title |
Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular Filtration |
title_short |
Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular Filtration |
title_full |
Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular Filtration |
title_fullStr |
Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular Filtration |
title_full_unstemmed |
Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular Filtration |
title_sort |
role of klotho in hyperglycemia: its levels and effects on fibroblast growth factor receptors, glycolysis, and glomerular filtration |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-07-01 |
description |
Hyperglycemic conditions (HG), at early stages of diabetic nephropathy (DN), cause a decrease in podocyte numbers and an aberration of their function as key cells for glomerular plasma filtration. Klotho protein was shown to overcome some negative effects of hyperglycemia. Klotho is also a coreceptor for fibroblast growth factor receptors (FGFRs), the signaling of which, together with a proper rate of glycolysis in podocytes, is needed for a proper function of the glomerular filtration barrier. Therefore, we measured levels of Klotho in renal tissue, serum, and urine shortly after DN induction. We investigated whether it influences levels of FGFRs, rates of glycolysis in podocytes, and albumin permeability. During hyperglycemia, the level of membrane-bound Klotho in renal tissue decreased, with an increase in the shedding of soluble Klotho, its higher presence in serum, and lower urinary excretion. The addition of Klotho increased FGFR levels, especially FGFR1/FGFR2, after their HG-induced decrease. Klotho also increased levels of glycolytic parameters of podocytes, and decreased podocytic and glomerular albumin permeability in HG. Thus, we found that the decrease in the urinary excretion of Klotho might be an early biomarker of DN and that Klotho administration may have several beneficial effects on renal function in DN. |
topic |
Klotho protein diabetes mellitus diabetic nephropathy hyperglycemia fibroblast growth factor receptors |
url |
https://www.mdpi.com/1422-0067/22/15/7867 |
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