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Impact of sex on diabetic nephropathy and the renal transcriptome in UNx db/db C57BLKS mice

Diabetic nephropathy (DN) is associated with albuminuria and loss of kidney function and is the leading cause of end‐stage renal disease. Despite evidence of sex‐associated differences in the progression of DN in human patients, male mice are predominantly being used in preclinical DN research and d...

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Autores principales: Sembach, Frederikke E., Fink, Lisbeth N., Johansen, Thea, Boland, Brandon B., Secher, Thomas, Thrane, Sebastian T., Nielsen, Jens C., Fosgerau, Keld, Vrang, Niels, Jelsing, Jacob, Pedersen, Tanja X., Østergaard, Mette V.
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/PMC6930935/
https://www.ncbi.nlm.nih.gov/pubmed/31876119
http://dx.doi.org/10.14814/phy2.14333
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author Sembach, Frederikke E.
Fink, Lisbeth N.
Johansen, Thea
Boland, Brandon B.
Secher, Thomas
Thrane, Sebastian T.
Nielsen, Jens C.
Fosgerau, Keld
Vrang, Niels
Jelsing, Jacob
Pedersen, Tanja X.
Østergaard, Mette V.
author_facet Sembach, Frederikke E.
Fink, Lisbeth N.
Johansen, Thea
Boland, Brandon B.
Secher, Thomas
Thrane, Sebastian T.
Nielsen, Jens C.
Fosgerau, Keld
Vrang, Niels
Jelsing, Jacob
Pedersen, Tanja X.
Østergaard, Mette V.
author_sort Sembach, Frederikke E.
collection PubMed
description Diabetic nephropathy (DN) is associated with albuminuria and loss of kidney function and is the leading cause of end‐stage renal disease. Despite evidence of sex‐associated differences in the progression of DN in human patients, male mice are predominantly being used in preclinical DN research and drug development. Here, we compared renal changes in male and female uninephrectomized (UNx) db/db C57BLKS mice using immunohistochemistry and RNA sequencing. Male and female UNx db/db mice showed similar progression of type 2 diabetes, as assessed by obesity, hyperglycemia, and HbA1c. Progression of DN was also similar between sexes as assessed by kidney and glomerular hypertrophy as well as urine albumin‐to‐creatinine ratio being increased in UNx db/db compared with control mice. In contrast, kidney collagen III and glomerular collagen IV were increased only in female UNx db/db as compared with respective control mice but showed a similar tendency in male UNx db/db mice. Comparison of renal cortex transcriptomes by RNA sequencing revealed 66 genes differentially expressed (p < .01) in male versus female UNx db/db mice, of which 9 genes were located on the sex chromosomes. In conclusion, male and female UNx db/db mice developed similar hallmarks of DN pathology, suggesting no or weak sex differences in the functional and structural changes during DN progression.
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spelling pubmed-69309352019-12-27 Impact of sex on diabetic nephropathy and the renal transcriptome in UNx db/db C57BLKS mice Sembach, Frederikke E. Fink, Lisbeth N. Johansen, Thea Boland, Brandon B. Secher, Thomas Thrane, Sebastian T. Nielsen, Jens C. Fosgerau, Keld Vrang, Niels Jelsing, Jacob Pedersen, Tanja X. Østergaard, Mette V. Physiol Rep Original Research Diabetic nephropathy (DN) is associated with albuminuria and loss of kidney function and is the leading cause of end‐stage renal disease. Despite evidence of sex‐associated differences in the progression of DN in human patients, male mice are predominantly being used in preclinical DN research and drug development. Here, we compared renal changes in male and female uninephrectomized (UNx) db/db C57BLKS mice using immunohistochemistry and RNA sequencing. Male and female UNx db/db mice showed similar progression of type 2 diabetes, as assessed by obesity, hyperglycemia, and HbA1c. Progression of DN was also similar between sexes as assessed by kidney and glomerular hypertrophy as well as urine albumin‐to‐creatinine ratio being increased in UNx db/db compared with control mice. In contrast, kidney collagen III and glomerular collagen IV were increased only in female UNx db/db as compared with respective control mice but showed a similar tendency in male UNx db/db mice. Comparison of renal cortex transcriptomes by RNA sequencing revealed 66 genes differentially expressed (p < .01) in male versus female UNx db/db mice, of which 9 genes were located on the sex chromosomes. In conclusion, male and female UNx db/db mice developed similar hallmarks of DN pathology, suggesting no or weak sex differences in the functional and structural changes during DN progression. John Wiley and Sons Inc. 2019-12-25 /pmc/articles/PMC6930935/ /pubmed/31876119 http://dx.doi.org/10.14814/phy2.14333 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
Sembach, Frederikke E.
Fink, Lisbeth N.
Johansen, Thea
Boland, Brandon B.
Secher, Thomas
Thrane, Sebastian T.
Nielsen, Jens C.
Fosgerau, Keld
Vrang, Niels
Jelsing, Jacob
Pedersen, Tanja X.
Østergaard, Mette V.
Impact of sex on diabetic nephropathy and the renal transcriptome in UNx db/db C57BLKS mice
title Impact of sex on diabetic nephropathy and the renal transcriptome in UNx db/db C57BLKS mice
title_full Impact of sex on diabetic nephropathy and the renal transcriptome in UNx db/db C57BLKS mice
title_fullStr Impact of sex on diabetic nephropathy and the renal transcriptome in UNx db/db C57BLKS mice
title_full_unstemmed Impact of sex on diabetic nephropathy and the renal transcriptome in UNx db/db C57BLKS mice
title_short Impact of sex on diabetic nephropathy and the renal transcriptome in UNx db/db C57BLKS mice
title_sort impact of sex on diabetic nephropathy and the renal transcriptome in unx db/db c57blks mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930935/
https://www.ncbi.nlm.nih.gov/pubmed/31876119
http://dx.doi.org/10.14814/phy2.14333
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