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N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models

Liljedahl, Leena LU ; Pedersen, Maiken Højgaard; Norlin, Jenny; McGuire, James N. and James, Peter LU (2016) In Clinical Proteomics 13(1).
Abstract

Background: Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. Method: We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. Glycopeptides were analyzed... (More)

Background: Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. Method: We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. Glycopeptides were analyzed with label-free shotgun mass spectrometry and differential protein abundances identified in both mouse models were compared using multivariate analyses. Results: The majority of the N-glycosylated proteins were similarly regulated in both mouse models. However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. Insulin had an effect on the level of both glomerular and tubular proteins in the db/db mice. It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. Conclusions: Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
db/db, Diabetic nephropathy, Glomerulus, Insulin, Mass spectrometry, N-glycosylation, N-linked glycosylation, Proximal tubules, STZ
in
Clinical Proteomics
volume
13
issue
1
publisher
Humana Press
external identifiers
  • scopus:84992199676
  • wos:000385315100001
ISSN
1542-6416
DOI
10.1186/s12014-016-9123-z
language
English
LU publication?
yes
id
a67d7f62-2d01-45bd-8087-a7f36e3414a2
date added to LUP
2016-11-15 14:08:01
date last changed
2017-11-19 04:34:50
@article{a67d7f62-2d01-45bd-8087-a7f36e3414a2,
  abstract     = {<p>Background: Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. Method: We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. Glycopeptides were analyzed with label-free shotgun mass spectrometry and differential protein abundances identified in both mouse models were compared using multivariate analyses. Results: The majority of the N-glycosylated proteins were similarly regulated in both mouse models. However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. Insulin had an effect on the level of both glomerular and tubular proteins in the db/db mice. It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. Conclusions: Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice.</p>},
  articleno    = {22},
  author       = {Liljedahl, Leena and Pedersen, Maiken Højgaard and Norlin, Jenny and McGuire, James N. and James, Peter},
  issn         = {1542-6416},
  keyword      = {db/db,Diabetic nephropathy,Glomerulus,Insulin,Mass spectrometry,N-glycosylation,N-linked glycosylation,Proximal tubules,STZ},
  language     = {eng},
  month        = {10},
  number       = {1},
  publisher    = {Humana Press},
  series       = {Clinical Proteomics},
  title        = {N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models},
  url          = {http://dx.doi.org/10.1186/s12014-016-9123-z},
  volume       = {13},
  year         = {2016},
}